K A Jacobson

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. ncbi Probing GPCR structure: adenosine and P2Y nucleotide receptors
    Kenneth A Jacobson
    Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
    Methods Enzymol 520:199-217. 2013
  2. ncbi Allosteric modulation of the adenosine family of receptors
    Zhan Guo Gao
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Inst of Health, Bethesda, Maryland 20892 0810, USA
    Mini Rev Med Chem 5:545-53. 2005
  3. ncbi Polyamidoamine (PAMAM) dendrimer conjugate specifically activates the A3 adenosine receptor to improve post-ischemic/reperfusion function in isolated mouse hearts
    Tina C Wan
    Department of Pharmacology Toxicology and the Cardiovascular Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    BMC Pharmacol 11:11. 2011
  4. ncbi Neoceptor concept based on molecular complementarity in GPCRs: a mutant adenosine A(3) receptor with selectively enhanced affinity for amine-modified nucleosides
    K A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Med Chem 44:4125-36. 2001
  5. ncbi Pharmacochemistry of the platelet purinergic receptors
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg 8A, Rm B1A 19, NIH, NIDDK, LBC, Bethesda, MD, 20892 0810, USA
    Purinergic Signal 7:305-24. 2011
  6. ncbi GPCR ligand-dendrimer (GLiDe) conjugates: future smart drugs?
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA
    Trends Pharmacol Sci 31:575-9. 2010
  7. ncbi P2Y nucleotide receptors: promise of therapeutic applications
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Drug Discov Today 15:570-8. 2010
  8. ncbi Nucleoside conjugates of quantum dots for characterization of G protein-coupled receptors: strategies for immobilizing A2A adenosine receptor agonists
    Arijit Das
    Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Nanobiotechnology 8:11. 2010
  9. ncbi Interactions of flavones and other phytochemicals with adenosine receptors
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes ofHealth, Bethesda, MD 20892 0810, USA
    Adv Exp Med Biol 505:163-71. 2002
  10. ncbi Synthesis and pharmacological characterization of [(125)I]MRS1898, a high-affinity, selective radioligand for the rat A(3) adenosine receptor
    Zhan Guo Gao
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
    Purinergic Signal 5:31-7. 2009

Collaborators

Detail Information

Publications145 found, 100 shown here

  1. ncbi Probing GPCR structure: adenosine and P2Y nucleotide receptors
    Kenneth A Jacobson
    Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
    Methods Enzymol 520:199-217. 2013
    ....
  2. ncbi Allosteric modulation of the adenosine family of receptors
    Zhan Guo Gao
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Inst of Health, Bethesda, Maryland 20892 0810, USA
    Mini Rev Med Chem 5:545-53. 2005
    ..Amiloride analogues, SCH-202676 (N-(2,3-diphenyl-1,2,4-thiadiazol-5(2H)-ylidene)methanamine), and sodium ions were demonstrated to be common allosteric modulators for at least three subtypes (A(1), A(2A), and A(3)) of ARs...
  3. ncbi Polyamidoamine (PAMAM) dendrimer conjugate specifically activates the A3 adenosine receptor to improve post-ischemic/reperfusion function in isolated mouse hearts
    Tina C Wan
    Department of Pharmacology Toxicology and the Cardiovascular Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    BMC Pharmacol 11:11. 2011
    ..We have examined pharmacologically the protective properties of a multivalent dendrimeric conjugate of a nucleoside as a selective multivalent agonist for the mouse A3AR...
  4. ncbi Neoceptor concept based on molecular complementarity in GPCRs: a mutant adenosine A(3) receptor with selectively enhanced affinity for amine-modified nucleosides
    K A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Med Chem 44:4125-36. 2001
    ..We have termed such engineered receptors "neoceptors", since the ligand recognition profile of such mutant receptors need not correspond to the profile of the parent, native receptor...
  5. ncbi Pharmacochemistry of the platelet purinergic receptors
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg 8A, Rm B1A 19, NIH, NIDDK, LBC, Bethesda, MD, 20892 0810, USA
    Purinergic Signal 7:305-24. 2011
    ..In conclusion, a wide range of new pharmacological tools is available to control platelet function by interacting with cell surface purine receptors...
  6. ncbi GPCR ligand-dendrimer (GLiDe) conjugates: future smart drugs?
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA
    Trends Pharmacol Sci 31:575-9. 2010
    ..The feasibility of targeting multiple adenosine and P2Y receptors for synergistic effects has been shown. Testing in vivo will be needed to explore the effects on pharmacokinetics and tissue targeting...
  7. ncbi P2Y nucleotide receptors: promise of therapeutic applications
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Drug Discov Today 15:570-8. 2010
    ..On the horizon are novel treatments for cardiovascular diseases, inflammatory diseases and neurodegeneration...
  8. ncbi Nucleoside conjugates of quantum dots for characterization of G protein-coupled receptors: strategies for immobilizing A2A adenosine receptor agonists
    Arijit Das
    Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Nanobiotechnology 8:11. 2010
    ..abstract:..
  9. ncbi Interactions of flavones and other phytochemicals with adenosine receptors
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes ofHealth, Bethesda, MD 20892 0810, USA
    Adv Exp Med Biol 505:163-71. 2002
    ..Adenosine receptor antagonism, therefore, may be important in the spectrum of biological activities reported for the flavonoids...
  10. ncbi Synthesis and pharmacological characterization of [(125)I]MRS1898, a high-affinity, selective radioligand for the rat A(3) adenosine receptor
    Zhan Guo Gao
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
    Purinergic Signal 5:31-7. 2009
    ..Thus, we have introduced the first selective radioligand for the rat A(3)AR...
  11. ncbi A3 adenosine receptors and mitogen-activated protein kinases in lung injury following in vivo reperfusion
    Idit Matot
    Department of Anesthesiology and Critical Care Medicine, Hadassah University Medical Center, The Hebrew University, Jerusalem, Israel
    Crit Care 10:R65. 2006
    ..In addition, we compared the effect of the A3 adenosine agonist IB-MECA with the newly synthesized, highly selective A3 adenosine receptor agonist MRS3558 on injury in reperfused lung...
  12. ncbi Adenosine receptors as therapeutic targets
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0810, USA
    Nat Rev Drug Discov 5:247-64. 2006
    ....
  13. ncbi Application of the functionalized congener approach to dendrimer-based signaling agents acting through A(2A) adenosine receptors
    Yoonkyung Kim
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
    Purinergic Signal 5:39-50. 2009
    ..The present study demonstrates the potential of applying the functionalized congener concept to engineer dendrimer-based multivalent ligands for G protein-coupled receptors...
  14. ncbi G protein-coupled adenosine (P1) and P2Y receptors: ligand design and receptor interactions
    Kenneth A Jacobson
    Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Purinergic Signal 8:419-36. 2012
    ....
  15. ncbi New insights for drug design from the X-ray crystallographic structures of G-protein-coupled receptors
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0810, USA
    Mol Pharmacol 82:361-71. 2012
    ....
  16. ncbi Pharmacological characterization of novel A3 adenosine receptor-selective antagonists
    K A Jacobson
    Molecular Recognition Section, LBC, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA
    Neuropharmacology 36:1157-65. 1997
    ..In addition, MRS 1220 reversed the effect of A3 agonist-elicited inhibition of tumor necrosis factor-alpha formation in the human macrophage U-937 cell line, with an IC50 value of 0.3 microM...
  17. ncbi A pyridoxine cyclic phosphate and its 6-azoaryl derivative selectively potentiate and antagonize activation of P2X1 receptors
    K A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892 0810, USA
    J Med Chem 41:2201-6. 1998
    ..Thus, compounds 2 and 3 are relatively selective pharmacological probes of P2X1 receptors, filling a long-standing need in the P2 receptor field, and are also important lead compounds for future studies...
  18. ncbi Methanocarba analogues of purine nucleosides as potent and selective adenosine receptor agonists
    K A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0810, USA
    J Med Chem 43:2196-203. 2000
    ..Partial agonism combined with high functional potency at A(3) receptors (EC(50) < 1 nM) may produce tissue selectivity. In conclusion, as for P2Y(1) receptors, at least three adenosine receptors favor the ribose (N)-conformation...
  19. ncbi In search of selective P2 receptor ligands: interaction of dihydropyridine derivatives at recombinant rat P2X(2) receptors
    K A Jacobson
    Molecular Recognition Section, Bldg 8A, Rm B1A 19, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892 0810, USA
    J Auton Nerv Syst 81:152-7. 2000
    ..Thus, while a conventional dihydropyridine, nicardipine, was found to antagonize rat P2X(2) receptors ninefold more potently than P2X(4) receptors, the effects of novel, anionic 5-phosphonate analogues at the receptor were more complex...
  20. ncbi A novel pharmacological approach to treating cardiac ischemia. Binary conjugates of A1 and A3 adenosine receptor agonists
    K A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 275:30272-9. 2000
    ..1 nm) dependent on expression of both receptors. Thus, co-activation of both adenosine A(1) and A(3) receptors by the binary A(1)/A(3) agonists represents a novel general cardioprotective approach for the treatment of myocardial ischemia...
  21. ncbi Structurally related nucleotides as selective agonists and antagonists at P2Y1 receptors
    K A Jacobson
    Molecular Recognition Section, LBC, NIDDK, National Institutes of Health, Bethesda, MD 20892 0810, USA
    Farmaco 56:71-5. 2001
    ..With simplified pharmacophores we are exploring the steric and electronic requirements of the receptor binding site, and the structural basis of receptor activation...
  22. ncbi Flexible modulation of agonist efficacy at the human A3 adenosine receptor by the imidazoquinoline allosteric enhancer LUF6000
    Zhan Guo Gao
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0810, USA
    BMC Pharmacol 8:20. 2008
    ..Here we studied the modulation by LUF6000 of the maximum effect (Emax) of structurally diverse agonists at the A3 AR stably expressed in CHO cells...
  23. ncbi Molecular recognition at purine and pyrimidine nucleotide (P2) receptors
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Biorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Disease, Bethesda, MD 20892 0810, USA E mail
    Curr Top Med Chem 4:805-19. 2004
    ..The binding of the negatively-charged phosphate moiety is dependent on positively charged lysine and arginine residues near the exofacial side of TMs 3 and 7...
  24. ncbi Neoceptors: reengineering GPCRs to recognize tailored ligands
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases NIDDK, National Institutes of Health NIH, Bethesda, MD 20892, USA
    Trends Pharmacol Sci 28:111-6. 2007
    ..The neoceptor-neoligand pairing could offer spatial specificity by delivering the neoceptor to a target site, and temporal specificity by administering neoligand when needed...
  25. ncbi Structure activity and molecular modeling analyses of ribose- and base-modified uridine 5'-triphosphate analogues at the human P2Y2 and P2Y4 receptors
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Biochem Pharmacol 71:540-9. 2006
    ....
  26. ncbi Development of selective agonists and antagonists of P2Y receptors
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg 8A, Rm B1A 19, Bethesda, MD, USA
    Purinergic Signal 5:75-89. 2009
    ..The continuing process of ligand design for the P2Y receptors will aid in the identification of new clinical targets...
  27. ncbi Enhanced A3 adenosine receptor selectivity of multivalent nucleoside-dendrimer conjugates
    Athena M Klutz
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA
    J Nanobiotechnology 6:12. 2008
    ..abstract:..
  28. ncbi A neoceptor approach to unraveling microscopic interactions between the human A2A adenosine receptor and its agonists
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Chem Biol 12:237-47. 2005
    ..Thus, we identified and modeled pairs of A(2A)AR-derived neoceptor-neoligand, which are pharmacologically orthogonal with respect to the native species...
  29. ncbi Action of nucleosides and nucleotides at 7 transmembrane-spanning receptors
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0810, USA
    Nucleosides Nucleotides Nucleic Acids 25:1425-36. 2006
    ..Using a rational design process we have identified neoceptor-neoligand pairs which are pharmacologically orthogonal with respect to the native species...
  30. ncbi Molecular recognition at adenine nucleotide (P2) receptors in platelets
    Kenneth A Jacobson
    Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0810, USA
    Semin Thromb Hemost 31:205-16. 2005
    ..The P2Y (1) receptor model, especially, has been exploited in the design and optimization of antagonists targeted to interact selectively with that subtype...
  31. ncbi Semi-rational design of (north)-methanocarba nucleosides as dual acting A(1) and A(3) adenosine receptor agonists: novel prototypes for cardioprotection
    Kenneth A Jacobson
    National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Med Chem 48:8103-7. 2005
    ..Consequently, 2 was balanced in affinity and potency at A(1)/A(3)ARs as envisioned and dramatically protected in an intact heart model of global ischemia and reperfusion...
  32. ncbi Hydrophilic side chains in the third and seventh transmembrane helical domains of human A2A adenosine receptors are required for ligand recognition
    Q Jiang
    Molecular Recognition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Pharmacol 50:512-21. 1996
    ..A S281N mutant gained affinity for all adenosine derivatives (agonists), but antagonist affinity was generally diminished, with the exception of a novel tetrahydrobenzothiophenone derivative...
  33. ncbi Structure-guided design of A(3) adenosine receptor-selective nucleosides: combination of 2-arylethynyl and bicyclo[3.1.0]hexane substitutions
    Dilip K Tosh
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, United States
    J Med Chem 55:4847-60. 2012
    ..Thus, the X-ray structure of related A(2A)AR is useful in guiding the design of new A(3)AR agonists...
  34. ncbi Evaluation of molecular modeling of agonist binding in light of the crystallographic structure of an agonist-bound A₂A adenosine receptor
    Francesca Deflorian
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 8A, Room B1A 19, Bethesda, Maryland 20892 0810, United States
    J Med Chem 55:538-52. 2012
    ..Amino acid moieties were coordinated close to extracellular loops 2 and 3. Thus, molecular modeling is useful in probing ligand recognition and rational design of GPCR-targeting compounds with specific pharmacological profiles...
  35. ncbi Ribose modified nucleosides and nucleotides as ligands for purine receptors
    K A Jacobson
    Molecular Recognition Section, LBC, NIDDK, National Inst. of Health, Bethesda, Maryland 20902, USA
    Nucleosides Nucleotides Nucleic Acids 20:333-41. 2001
    ..e. fused cyclopropane and cyclopentane rings in place of ribose, suggesting a preference for the Northern (N) conformation among ligands for P2Y1 and A1 and A3ARs...
  36. ncbi Optimization of adenosine 5'-carboxamide derivatives as adenosine receptor agonists using structure-based ligand design and fragment screening
    Dilip K Tosh
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Med Chem 55:4297-308. 2012
    ..The study suggests further applicability of in silico fragment screening to rational lead optimization in GPCRs...
  37. ncbi Functionally biased modulation of A(3) adenosine receptor agonist efficacy and potency by imidazoquinolinamine allosteric enhancers
    Zhan Guo Gao
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0810, USA
    Biochem Pharmacol 82:658-68. 2011
    ..The differential effects of LUF6000 on the efficacy and potency of the agonist Cl-IB-MECA in various signaling pathway were interpreted quantitatively using a mathematical model...
  38. ncbi A missense mutation in the seven-transmembrane domain of the human Ca2+ receptor converts a negative allosteric modulator into a positive allosteric modulator
    Jianxin Hu
    Molecular Pathophysiology Section, NIDCD, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 281:21558-65. 2006
    ..Our results suggest the need for identification of possible genetic variation in the allosteric site of therapeutically targeted GPCRs...
  39. ncbi Structure-activity relationships of pyridoxal phosphate derivatives as potent and selective antagonists of P2X1 receptors
    Y C Kim
    Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892-0810, USA
    J Med Chem 44:340-9. 2001
    ..None of the analogues were more potent at P2X7 and P2Y1 receptors than 2, which acted in the micromolar range at these two subtypes...
  40. ncbi Modulation of adenosine receptor affinity and intrinsic efficacy in adenine nucleosides substituted at the 2-position
    Michihiro Ohno
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH, DHHS, Bldg. 8A, Rm. B1A-19, NIH, NIDDK, LBC, Bethesda, MD 20892-0810, USA
    Bioorg Med Chem 12:2995-3007. 2004
    ..The environment surrounding the 2-position within the putative A(3)AR binding site was explored using rhodopsin-based homology modeling and ligand docking...
  41. ncbi Novel fluorescent antagonist as a molecular probe in A(3) adenosine receptor binding assays using flow cytometry
    Eszter Kozma
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0810, USA
    Biochem Pharmacol 83:1552-61. 2012
    ..Further binding analysis of MRS5549 suggested multiple agonist binding states of the A(3)AR. Molecular docking predicted binding modes of these fluorescent antagonists. Thus, MRS5449 is a useful tool for hA(3)AR characterization...
  42. ncbi Pyrimidine ribonucleotides with enhanced selectivity as P2Y(6) receptor agonists: novel 4-alkyloxyimino, (S)-methanocarba, and 5'-triphosphate gamma-ester modifications
    Hiroshi Maruoka
    Molecular Recognition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
    J Med Chem 53:4488-501. 2010
    ..47 and 0.18 microM, respectively). Thus, the potency, selectivity, and stability of pyrimidine nucleotides as P2Y(6) receptor agonists may be enhanced by modest structural changes...
  43. ncbi Trifunctional agents as a design strategy for tailoring ligand properties: irreversible inhibitors of A1 adenosine receptors
    D L Boring
    Laboratory of Bioorganic Chemistry, National Institute of Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892
    Bioconjug Chem 2:77-88. 1991
    ....
  44. ncbi Structure-activity relationships of 1,3-dialkylxanthine derivatives at rat A3 adenosine receptors
    H O Kim
    Molecular Recognition Section, National Institute of Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892
    J Med Chem 37:3373-82. 1994
    ..1,3,7-Trimethyl-8-(trans-2-carboxyvinyl)xanthine was somewhat selective for A3 vs A1 receptors. For 8-arylxanthines affinity at A3 receptors was enhanced by 1,3-dialkyl substituents, in the order dibutyl > dipropyl > diallyl...
  45. ncbi Probing the binding site of the A1 adenosine receptor reengineered for orthogonal recognition by tailored nucleosides
    Krishnan K Palaniappan
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0810, USA
    Biochemistry 46:7437-48. 2007
    ..This neoceptor approach should be useful for the validation of molecular modeling and the dissection of promiscuous GPCR signaling...
  46. ncbi Regulation of death and survival in astrocytes by ADP activating P2Y1 and P2Y12 receptors
    Liaman K Mamedova
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0810, USA
    Biochem Pharmacol 72:1031-41. 2006
    ..These results may have important implications for understanding the signaling cascades that follow activation of P2Y(1) and P2Y(12) receptors and their opposing effects on cell death pathways...
  47. ncbi PEGylated dendritic unimolecular micelles as versatile carriers for ligands of G protein-coupled receptors
    Yoonkyung Kim
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Bioconjug Chem 20:1888-98. 2009
    ..The current study demonstrates the feasibility of using short PEG chains in the design of carriers that target ligand-receptor interactions...
  48. ncbi A region in the seven-transmembrane domain of the human Ca2+ receptor critical for response to Ca2+
    Jianxin Hu
    Molecular Pathophysiology Section, NIDCD, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 280:5113-20. 2005
    ..The implications of our finding that NPS 2143 corrects the molecular defect of ADH mutations for treatment of this disease are also discussed...
  49. ncbi Ring-Constrained (N)-methanocarba nucleosides as adenosine receptor agonists: independent 5'-uronamide and 2'-deoxy modifications
    K Lee
    Molecular Recognition Section, LBC, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA
    Bioorg Med Chem Lett 11:1333-7. 2001
    ..The 5'-uronamide modification preserved [N6-(3-iodobenzyl)] or enhanced (N6-methyl) affinity at A3ARs, while the 2'-deoxy modification reduced affinity and efficacy in a functional assay...
  50. ncbi Acyclic and cyclopropyl analogues of adenosine bisphosphate antagonists of the P2Y1 receptor: structure-activity relationships and receptor docking
    H S Kim
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0810, USA
    J Med Chem 44:3092-108. 2001
    ..In summary, modification of the flexible spacer chain linking bisphosphate groups to the adenine moiety provided many moderately potent antagonists...
  51. ncbi Synthesis and purine receptor affinity of 6-oxopurine nucleosides and nucleotides containing (N)-methanocarba-pseudoribose rings
    G Ravi
    Molecular Recognition Section, LBC, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA
    Bioorg Med Chem Lett 11:2295-300. 2001
    ..Guanine or hypoxanthine was coupled at the 7-position, or 1,3-dibutylxanthine was coupled at the 9-position. The pseudoribose ring was also substituted at the 5'-position with an N-methyluronamide or with phosphate groups...
  52. ncbi Click modification in the N6 region of A3 adenosine receptor-selective carbocyclic nucleosides for dendrimeric tethering that preserves pharmacophore recognition
    Dilip K Tosh
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Bioconjug Chem 23:232-47. 2012
    ..Thus, the N(6) region of 5'-methyluronamide derivatives, as modeled in receptor docking, is suitable for functionalization and tethering by click chemistry to achieve high A(3)AR agonist affinity and enhanced selectivity...
  53. ncbi Structure-activity relationships of uridine 5'-diphosphate analogues at the human P2Y6 receptor
    Pedro Besada
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Med Chem 49:5532-43. 2006
    ..These results provide a better understanding of molecular recognition at the P2Y6 receptor and will be helpful in designing selective and potent P2Y6 receptor ligands...
  54. ncbi Caged agonist of P2Y1 and P2Y12 receptors for light-directed facilitation of platelet aggregation
    Zhan Guo Gao
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 8A, Room B1A 19, Bethesda, MD 20892 0810, USA
    Biochem Pharmacol 75:1341-7. 2008
    ..At 1.0 microM MRS2703, full aggregation was achieved within 1 min of irradiation. Thus, this caged nucleotide promises to be a useful probe for potent P2Y receptor activation with light-directed spatial and temporal control...
  55. ncbi Rapid identification of functionally critical amino acids in a G protein-coupled receptor
    Bo Li
    Molecular Signaling, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA
    Nat Methods 4:169-74. 2007
    ..The screening strategy described here should be applicable to all GPCRs that can be expressed functionally in yeast...
  56. ncbi Agonists and antagonists for P2 receptors
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0810, USA
    Novartis Found Symp 276:58-68; discussion 68-72, 107-12, 275-81. 2006
    ..Three-dimensional structures of P2Y receptors have been deduced from structure activity relationships (SAR), mutagenesis and modelling studies. Detailed three-dimensional structures of P2X receptors have not yet been proposed...
  57. ncbi Human P2Y(6) receptor: molecular modeling leads to the rational design of a novel agonist based on a unique conformational preference
    Stefano Costanzi
    NIDDK, National Institutes of Health, DHHS, Bethesda, Maryland 20892 USA
    J Med Chem 48:8108-11. 2005
    ..MD results also suggested a conformational change of the second extracellular loop consequent to agonist binding...
  58. ncbi P2Y6 nucleotide receptor activates PKC to protect 1321N1 astrocytoma cells against tumor necrosis factor-induced apoptosis
    Seong G Kim
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0810, USA
    Cell Mol Neurobiol 23:401-18. 2003
    ..6. The addition of phospholipase C (PLC) inhibitors, D609 or U73122, partially antagonized both UDP-induced protection and PKC activation...
  59. ncbi Constitutive activation of A(3) adenosine receptors by site-directed mutagenesis
    A Chen
    Molecular Recognition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Biochem Biophys Res Commun 284:596-601. 2001
    ..The results indicated that specific locations within the TMs proximal to the cytosolic region were responsible for constraining the receptor in a G protein-uncoupled conformation...
  60. ncbi Pronounced conformational changes following agonist activation of the M(3) muscarinic acetylcholine receptor
    Sung Jun Han
    Molecular Signaling Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 280:24870-9. 2005
    ..These findings should be of relevance for other family A GPCRs...
  61. ncbi Identification of an agonist-induced conformational change occurring adjacent to the ligand-binding pocket of the M(3) muscarinic acetylcholine receptor
    Sung Jun Han
    Molecular Signaling and Molecular Recognition Sections, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 0810, USA
    J Biol Chem 280:34849-58. 2005
    ..To the best of our knowledge, this is the first direct demonstration of a conformational change occurring in the immediate vicinity of the binding site of a GPCR activated by a diffusible ligand...
  62. ncbi GPCR ligand dendrimer (GLiDe) conjugates: adenosine receptor interactions of a series of multivalent xanthine antagonists
    Angela Kecskés
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, United States
    Bioconjug Chem 22:1115-27. 2011
    ..This is the first systematic probing of a potent AR antagonist tethered on a dendrimer and its activity as a function of variable loading...
  63. ncbi Striatal adenosine A(2A) receptor-mediated positron emission tomographic imaging in 6-hydroxydopamine-lesioned rats using [(18)F]-MRS5425
    Abesh Kumar Bhattacharjee
    Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA
    Nucl Med Biol 38:897-906. 2011
    ....
  64. ncbi Synthesis and characterization of [76Br]-labeled high-affinity A3 adenosine receptor ligands for positron emission tomography
    Dale O Kiesewetter
    Positron Emission Tomography Radiochemistry Group, NIBIB, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
    Nucl Med Biol 36:3-10. 2009
    ..Bromine-76-radiolabeled analogues of previously reported high-affinity A(3) adenosine receptor (A(3)AR) nucleoside ligands have been prepared as potential radiotracers for positron emission tomography...
  65. ncbi Conformational changes involved in G-protein-coupled-receptor activation
    Jurgen Wess
    Molecular Signaling Section and Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Trends Pharmacol Sci 29:616-25. 2008
    ..A better understanding of the molecular mechanisms underlying GPCR activation might lead to novel strategies aimed at modulating GPCR function for therapeutic purposes...
  66. ncbi Functionalized congeners of P2Y1 receptor antagonists: 2-alkynyl (N)-methanocarba 2'-deoxyadenosine 3',5'-bisphosphate analogues and conjugation to a polyamidoamine (PAMAM) dendrimer carrier
    Sonia de Castro
    Molecular Recognition Section and Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, 20892 0810, USA
    Bioconjug Chem 21:1190-205. 2010
    ..This is the first example of attaching a strategically functionalized P2Y receptor antagonist to a PAMAM dendrimer to produce a multivalent conjugate exhibiting a desired biological effect, i.e., antithrombotic action...
  67. ncbi Docking studies of agonists and antagonists suggest an activation pathway of the A3 adenosine receptor
    Soo-Kyung Kim
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, National Institutes of Health (NIH, Bethesda, MD 20892, USA
    J Mol Graph Model 25:562-77. 2006
    ..Thus, the putative conformational changes associated with A(3)AR activation indicate a shared mechanism of GPCR activation similar to rhodopsin...
  68. ncbi Exploring distal regions of the A3 adenosine receptor binding site: sterically constrained N6-(2-phenylethyl)adenosine derivatives as potent ligands
    Susanna Tchilibon
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health, and Human Services, Bethesda, MD 20892-0810, USA
    Bioorg Med Chem 12:2021-34. 2004
    ..Thus, a new series of high-affinity A(3)AR agonists and related nucleoside antagonists was explored through both empirical and theoretical approaches...
  69. ncbi Modelling the P2Y purinoceptor using rhodopsin as template
    A M van Rhee
    NIH, NIDDK, LBC, Molecular Recognition Section, Bethesda, Maryland 20892 0810, USA
    Drug Des Discov 13:133-54. 1995
    ....
  70. ncbi Selective allosteric enhancement of agonist binding and function at human A3 adenosine receptors by a series of imidazoquinoline derivatives
    Zhan-Guo Gao
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0810, USA
    Mol Pharmacol 62:81-9. 2002
    ..Thus, we have identified a novel structural lead for developing allosteric enhancers of A3 adenosine receptors; such enhancers may be useful for treating brain ischemia and other hypoxic conditions...
  71. ncbi Probing distal regions of the A2B adenosine receptor by quantitative structure-activity relationship modeling of known and novel agonists
    Andrei A Ivanov
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Med Chem 51:2088-99. 2008
    ..Thus, in support of the modeling, bulky substitutions at both positions did not prevent A 2B AR activation, which predicts separate regions for docking of these moieties...
  72. ncbi Differential allosteric modulation by amiloride analogues of agonist and antagonist binding at A(1) and A(3) adenosine receptors
    Zhan-Guo Gao
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK/National Institutes of Health, Bldg. 8A, Rm. B1A-19, Bethesda, MD 20892-0810, USA
    Biochem Pharmacol 65:525-34. 2003
    ..Both binding and functional assays support the allosteric interactions of amiloride analogues with A(3) receptors...
  73. ncbi Structural determinants of A(3) adenosine receptor activation: nucleoside ligands at the agonist/antagonist boundary
    Zhan-Guo Gao
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Med Chem 45:4471-84. 2002
    ..Thus, A(3)AR activation appeared to require flexibility at the 5'- and 3'-positions, which was diminished in (N)-methanocarba, spiro, and epoxide analogues, and was characteristic of ribose interactions at TM6 and TM7...
  74. ncbi Allosteric modulation of A(3) adenosine receptors by a series of 3-(2-pyridinyl)isoquinoline derivatives
    Z G Gao
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Pharmacol 60:1057-63. 2001
    ....
  75. ncbi Selective A(3) adenosine receptor antagonists derived from nucleosides containing a bicyclo[3.1.0]hexane ring system
    Artem Melman
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 8A, Room B1A 19, Bethesda, MD 20892, USA
    Bioorg Med Chem 16:8546-56. 2008
    ..7-1.4 nM. In a functional assay of [35S]GTPcS binding, 33b (3-iodobenzyl) completely inhibited stimulation by NECA with a KB of 8.9 nM. Thus, a highly potent and selective series of A3AR antagonists has been described...
  76. ncbi Design of (N)-methanocarba adenosine 5'-uronamides as species-independent A3 receptor-selective agonists
    Artem Melman
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 8A, Room B1A 19, Bethesda, MD 20892 0810, USA
    Bioorg Med Chem Lett 18:2813-9. 2008
    ..Extended and chemically functionalized alkynyl chains attached at the C2 position of the purine moiety preserved A(3)AR selectivity more effectively than similar chains attached at the 3-position of the N(6)-benzyl group...
  77. ncbi Adenine nucleotide analogues locked in a Northern methanocarba conformation: enhanced stability and potency as P2Y(1) receptor agonists
    R Gnana Ravi
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases/NIH, Building 8A, Room B1A-17, Bethesda, MD 20892-0810, USA
    J Med Chem 45:2090-100. 2002
    ..This suggests that new, more stable and selective nucleotide agonists may be designed on the basis of the (N)-conformation, which greatly enhanced potency at P2Y(1) receptors...
  78. ncbi 2-Substitution of adenine nucleotide analogues containing a bicyclo[3.1.0]hexane ring system locked in a northern conformation: enhanced potency as P2Y1 receptor antagonists
    Hak Sung Kim
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-0810, USA
    J Med Chem 46:4974-87. 2003
    ..An enzymatic method of synthesis of the 3',5'-bisphosphate from the corresponding 3'-monophosphate, suitable for the preparation of a radiophosphorylated analogue, was explored...
  79. ncbi (N)-methanocarba 2,N6-disubstituted adenine nucleosides as highly potent and selective A3 adenosine receptor agonists
    Susanna Tchilibon
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Med Chem 48:1745-58. 2005
    ..Thus, many of the previously known groups that enhance A(3)AR affinity in the 9-riboside series, including those that reduce intrinsic efficacy, may be adapted to the (N)-methanocarba nucleoside series of full agonists...
  80. ncbi Adenosine analogs with covalently attached lipids have enhanced potency at A1-adenosine receptors
    K A Jacobson
    Laboratory of Chemistry, NIDDK, Bethesda, MD 20892
    FEBS Lett 225:97-102. 1987
    ..The very high affinity of adenosine-lipid conjugates may be due to stabilization of these adducts in the phospholipid microenvironment of the receptor protein...
  81. ncbi Identification of essential residues involved in the allosteric modulation of the human A(3) adenosine receptor
    Zhan Guo Gao
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892 0810, USA
    Mol Pharmacol 63:1021-31. 2003
    ..1-i]purin-5-one (PSB-11) at the WT A(3)ARs, but not the D58N(2.50) mutant receptor. The results were interpreted using a rhodopsin-based molecular model of the A(3)AR to suggest multiple binding modes of the allosteric modulators...
  82. ncbi Functionalized congeners of A3 adenosine receptor-selective nucleosides containing a bicyclo[3.1.0]hexane ring system
    Dilip K Tosh
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Med Chem 52:7580-92. 2009
    ..SAR parallels between the two series lost stringency at distal positions. The most potent and selective novel compounds were amine congener 15 (K(i) = 2.1 nM) and truncated partial agonist 22 (K(i) = 4.9 nM)...
  83. ncbi Ligand-specific changes in M3 muscarinic acetylcholine receptor structure detected by a disulfide scanning strategy
    Jian Hua Li
    Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases NIDDK, 8 Center Drive, Bethesda, Maryland 20892 0810, USA
    Biochemistry 47:2776-88. 2008
    ..Because all class I GPCRs are predicted to share a similar transmembrane topology, the conclusions drawn from the present study should be of broad general relevance...
  84. ncbi Evaluation of homology modeling of G-protein-coupled receptors in light of the A(2A) adenosine receptor crystallographic structure
    Andrei A Ivanov
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Med Chem 52:3284-92. 2009
    ..Thus, homology modeling of GPCRs remains a useful technique in probing the structure of the protein and predicting modes of ligand docking...
  85. ncbi Structure-activity relationships of 2,N(6),5'-substituted adenosine derivatives with potent activity at the A2B adenosine receptor
    Hayamitsu Adachi
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0810, USA
    J Med Chem 50:1810-27. 2007
    ..Compound 28 was a full agonist at A2B and A2AARs and a low efficacy partial agonist at A1 and A3ARs. Thus, we have identified and optimized 2-(2-arylethyl)oxo moieties in AR agonists that enhance A2BAR potency and selectivity...
  86. ncbi Effects of the allosteric modulator SCH-202676 on adenosine and P2Y receptors
    Zhan-Guo Gao
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bldg. 8A, Rm. B1A-19, Bethesda, MD 20892-0810, USA
    Life Sci 74:3173-80. 2004
    ..Thus, SCH-202676 differentially modulated A(1), A(2A), and A(3) receptors as well as agonist- and antagonist-occupied receptors...
  87. ncbi 2-Dialkynyl derivatives of (N)-methanocarba nucleosides: 'Clickable' A(3) adenosine receptor-selective agonists
    Dilip K Tosh
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg 8A, Rm B1A 19, NIH, NIDDK, LBC, Bethesda, MD 20892, United States
    Bioorg Med Chem 18:508-17. 2010
    ..Thus, this strategy provides a general chemical approach to linking potent and selective A(3)AR agonists to reporter groups of diverse structure and to carrier moieties...
  88. ncbi "Reversine" and its 2-substituted adenine derivatives as potent and selective A3 adenosine receptor antagonists
    Melissa Perreira
    Chemical Biology Core Facility, and Molecular Recognition Section, Laboratory of Biological Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Med Chem 48:4910-8. 2005
    ..We were unable to reproduce the dedifferentiation effect of reversine, previously reported, or to demonstrate any connection between A(3) AR antagonist effects and dedifferentiation...
  89. ncbi 2-Substituted adenosine derivatives: affinity and efficacy at four subtypes of human adenosine receptors
    Zhan-Guo Gao
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Biochem Pharmacol 68:1985-93. 2004
    ..4 microM) and 2-[2-(2-thienyl)-ethyloxy]adenosine (EC(50) = 1.8 microM) were found to be relatively potent A(2B) agonists, although less potent than NECA (EC(50) = 140 nM)...
  90. ncbi Architecture of P2Y nucleotide receptors: structural comparison based on sequence analysis, mutagenesis, and homology modeling
    Stefano Costanzi
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0810, USA
    J Med Chem 47:5393-404. 2004
    ..35. Thus, we have identified common and distinguishing features of P2Y receptor structure and have proposed modes of ligand binding for the two representative subtypes that already have well-developed ligands...
  91. ncbi [3H]MRS 1754, a selective antagonist radioligand for A(2B) adenosine receptors
    X Ji
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bldg. 8A, Room B1A-19, Bethesda, MD 20892, USA
    Biochem Pharmacol 61:657-63. 2001
    ..NECA (5'-N-ethylcarboxamidoadenosine) competed for [3H]MRS 1754 binding with a K(i) of 570 nM, similar to its potency in functional assays. Thus, [3H]MRS 1754 is suitable as a selective, high-affinity radioligand for A(2B) receptors...
  92. ncbi Synthesis of ethyl (1S,2R,3S,4S,5S)-2,3-O-(isopropylidene)-4-hydroxy-bicyclo[3.1.0]hexane-carboxylate from L-ribose: a versatile chiral synthon for preparation of adenosine and P2 receptor ligands
    Bhalchandra V Joshi
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892 0810, USA
    Nucleosides Nucleotides Nucleic Acids 27:279-91. 2008
    ..Improvements were made in subsequent steps corresponding to a published route to biologically important (N)-methanocarba 5'-uronamido nucleosides, and new steps were added to prepare related 5'-nucleotides...
  93. ncbi Molecular dynamics simulation of the P2Y14 receptor. Ligand docking and identification of a putative binding site of the distal hexose moiety
    Andrei A Ivanov
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Bioorg Med Chem Lett 17:761-6. 2007
    ..55) and Lys277 (7.35) of the P2Y14 receptor together with two anionic residues (Glu166 and Glu174, located in EL2), are likely involved in interactions with the distal hexose moiety...
  94. ncbi 2,2'-Pyridylisatogen tosylate antagonizes P2Y1 receptor signaling without affecting nucleotide binding
    Zhan-Guo Gao
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0810, USA
    Biochem Pharmacol 68:231-7. 2004
    ..Thus, PIT selectively and non-competitively blocked P2Y(1) receptor signaling without affecting nucleotide binding...
  95. ncbi Novel 2- and 4-substituted 1H-imidazo[4,5-c]quinolin-4-amine derivatives as allosteric modulators of the A3 adenosine receptor
    Yoonkyung Kim
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Med Chem 52:2098-108. 2009
    ....
  96. ncbi Molecular recognition in the P2Y(14) receptor: Probing the structurally permissive terminal sugar moiety of uridine-5'-diphosphoglucose
    Hyojin Ko
    Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg 8A, Rm B1A 19, Bethesda, MD 20892, USA
    Bioorg Med Chem 17:5298-311. 2009
    ..1.0]hexane groups abolished activity. Uridine-5'-diphosphoglucose also activates the P2Y(2) receptor, but the 2-thio analogue and several of the potent modified-glucose analogues were P2Y(14)-selective...
  97. ncbi Polyamidoamine (PAMAM) dendrimer conjugates of "clickable" agonists of the A3 adenosine receptor and coactivation of the P2Y14 receptor by a tethered nucleotide
    Dilip K Tosh
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Bioconjug Chem 21:372-84. 2010
    ..Synergistic effects of activating multiple GPCRs with a single dendrimer conjugate might be useful in disease treatment...
  98. ncbi Random mutagenesis of the M3 muscarinic acetylcholine receptor expressed in yeast: identification of second-site mutations that restore function to a coupling-deficient mutant M3 receptor
    Bo Li
    Department of Molecular Signaling, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, 8 Center Dr, Bethesda, MD 20892, USA
    J Biol Chem 280:5664-75. 2005
    ..Our data suggest a conformational link between the highly conserved Asp-113, Arg-165, and Tyr-250 residues which is critical for receptor activation...
  99. ncbi Structure-activity relationships at human and rat A2B adenosine receptors of xanthine derivatives substituted at the 1-, 3-, 7-, and 8-positions
    Soon-Ai Kim
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Med Chem 45:2131-8. 2002
    ..In conclusion, new leads for the design of xanthines substituted in the 1-, 3-, 7-, and 8-positions as A2B receptor-selective antagonists have been identified...
  100. ncbi Methanocarba modification of uracil and adenine nucleotides: high potency of Northern ring conformation at P2Y1, P2Y2, P2Y4, and P2Y11 but not P2Y6 receptors
    Hak Sung Kim
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0810, USA
    J Med Chem 45:208-18. 2002
    ..Our results suggest that new nucleotide agonists may be designed on the basis of the (N) conformation that favors selectivity for P2Y1, P2Y2, P2Y4, and P2Y11 receptors...
  101. ncbi Structural determinants of efficacy at A3 adenosine receptors: modification of the ribose moiety
    Zhan-Guo Gao
    Laboratory of Bioorganic Chemistry, Molecular Recognition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Biochem Pharmacol 67:893-901. 2004
    ....