M M Rosenkilde

Summary

Affiliation: Laboratory for Molecular Pharmacology
Country: Denmark

Publications

  1. ncbi Molecular mechanism of action of monocyclam versus bicyclam non-peptide antagonists in the CXCR4 chemokine receptor
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, The Panum Institute, University of Copenhagen, Copenhagen DK 2200, Denmark
    J Biol Chem 282:27354-65. 2007
  2. ncbi Molecular mechanism of AMD3100 antagonism in the CXCR4 receptor: transfer of binding site to the CXCR3 receptor
    Mette M Rosenkilde
    Department of Pharmacology, University of Copenhagen, The Panum Institute, DK 2200 Copenhagen, Denmark
    J Biol Chem 279:3033-41. 2004
  3. ncbi The chemokine system -- a major regulator of angiogenesis in health and disease
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute, Copenhagen, Denmark
    APMIS 112:481-95. 2004
  4. ncbi Virus-encoded chemokine receptors--putative novel antiviral drug targets
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute, University of Copenhagen, Buildn 18 6, Blegdamsvej 3, 2200 Copenhagen N, Denmark
    Neuropharmacology 48:1-13. 2005
  5. ncbi High constitutive activity of a virus-encoded seven transmembrane receptor in the absence of the conserved DRY motif (Asp-Arg-Tyr) in transmembrane helix 3
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute 18 6, Blegdamsvej 3, 2200 Copenhagen N, Denmark
    Mol Pharmacol 68:11-9. 2005
  6. ncbi Molecular pharmacological phenotyping of EBI2. An orphan seven-transmembrane receptor with constitutive activity
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, University of Copenhagen, Denmark
    J Biol Chem 281:13199-208. 2006
  7. ncbi Conformational constraining of inactive and active States of a seven transmembrane receptor by metal ion site engineering in the extracellular end of transmembrane segment V
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute, University of Copenhagen, Denmark
    Mol Pharmacol 70:1892-901. 2006
  8. ncbi Targeting herpesvirus reliance of the chemokine system
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, Panum Institute, University of Copenhagen, Copenhagen, Denmark
    Curr Drug Targets 7:103-18. 2006
  9. ncbi Potency of ligands correlates with affinity measured against agonist and inverse agonists but not against neutral ligand in constitutively active chemokine receptor
    M M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute, University of Copenhagen, DK 2200 Copenhagen, Denmark
    Mol Pharmacol 57:602-9. 2000
  10. ncbi GluVII:06--a highly conserved and selective anchor point for non-peptide ligands in chemokine receptors
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute, Copenhagen University, Denmark
    Curr Top Med Chem 6:1319-33. 2006

Collaborators

Detail Information

Publications46

  1. ncbi Molecular mechanism of action of monocyclam versus bicyclam non-peptide antagonists in the CXCR4 chemokine receptor
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, The Panum Institute, University of Copenhagen, Copenhagen DK 2200, Denmark
    J Biol Chem 282:27354-65. 2007
    ..It is suggested that the remaining cyclam ring of AMD3465, which ensures the efficacious blocking of the receptor, in a similar manner can be replaced by chemical moieties allowing for, for example, oral bioavailability...
  2. ncbi Molecular mechanism of AMD3100 antagonism in the CXCR4 receptor: transfer of binding site to the CXCR3 receptor
    Mette M Rosenkilde
    Department of Pharmacology, University of Copenhagen, The Panum Institute, DK 2200 Copenhagen, Denmark
    J Biol Chem 279:3033-41. 2004
    ..We suggest that non-peptide antagonists with, for example, improved oral bioavailability can be designed to mimic this interaction and thereby efficiently and selectively block the CXCR4 receptor...
  3. ncbi The chemokine system -- a major regulator of angiogenesis in health and disease
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute, Copenhagen, Denmark
    APMIS 112:481-95. 2004
    ....
  4. ncbi Virus-encoded chemokine receptors--putative novel antiviral drug targets
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute, University of Copenhagen, Buildn 18 6, Blegdamsvej 3, 2200 Copenhagen N, Denmark
    Neuropharmacology 48:1-13. 2005
    ..as novel antiviral strategies--will be highlighted here together with the potentials of the virus-encoded chemokines and chemokine-binding proteins as novel anti-inflammatory biopharmaceutical strategies...
  5. ncbi High constitutive activity of a virus-encoded seven transmembrane receptor in the absence of the conserved DRY motif (Asp-Arg-Tyr) in transmembrane helix 3
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute 18 6, Blegdamsvej 3, 2200 Copenhagen N, Denmark
    Mol Pharmacol 68:11-9. 2005
    ..It is concluded that the Arg of the DRY motif in transmembrane helix 3 is not essential for G protein coupling based on the constitutive as well as the ligand-mediated activity observed for ORF74-EHV2...
  6. ncbi Molecular pharmacological phenotyping of EBI2. An orphan seven-transmembrane receptor with constitutive activity
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, University of Copenhagen, Denmark
    J Biol Chem 281:13199-208. 2006
    ..3. Based on the constitutive signaling and cellular expression pattern of EBI2, it is suggested that it may function in conjunction with BILF1 in the reprogramming of the cell during EBV infection...
  7. ncbi Conformational constraining of inactive and active States of a seven transmembrane receptor by metal ion site engineering in the extracellular end of transmembrane segment V
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute, University of Copenhagen, Denmark
    Mol Pharmacol 70:1892-901. 2006
    ..Based on the complex action of Zn(II) and on the chemokine interaction for [R208H;R212H]-ORF74, we conclude that the extracellular end of TM-V is important for the activation of this CXC-chemokine receptor...
  8. ncbi Targeting herpesvirus reliance of the chemokine system
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, Panum Institute, University of Copenhagen, Copenhagen, Denmark
    Curr Drug Targets 7:103-18. 2006
    ..Therefore, blocking the signaling of these receptors will provide an efficient and highly specific way to inhibit viral replication in vivo and disease progression in the hosts...
  9. ncbi Potency of ligands correlates with affinity measured against agonist and inverse agonists but not against neutral ligand in constitutively active chemokine receptor
    M M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute, University of Copenhagen, DK 2200 Copenhagen, Denmark
    Mol Pharmacol 57:602-9. 2000
    ....
  10. ncbi GluVII:06--a highly conserved and selective anchor point for non-peptide ligands in chemokine receptors
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute, Copenhagen University, Denmark
    Curr Top Med Chem 6:1319-33. 2006
    ..It is envisioned that knowledge of this binding mode can be exploited in structure-based discovery and design of novel chemokine receptor ligands and especially ligands with specifically optimized properties...
  11. doi Structural motifs of importance for the constitutive activity of the orphan 7TM receptor EBI2: analysis of receptor activation in the absence of an agonist
    Tau Benned-Jensen
    Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, The Panum Institute, Copenhagen University, Blegdamsvej 2, 2200 Copenhagen, Denmark
    Mol Pharmacol 74:1008-21. 2008
    ....
  12. pmc Molecular requirements for inhibition of the chemokine receptor CCR8--probe-dependent allosteric interactions
    P C Rummel
    Department of Neuroscience and Pharmacology, Faculty of Health Sciences, Copenhagen University, Copenhagen, Denmark
    Br J Pharmacol 167:1206-17. 2012
    ..This structure differs from the predominant pharmacophore for most small-molecule CC-chemokine receptor antagonists, which in fact activate CCR8, suggesting that CCR8 inhibition requires alternative structural probes...
  13. ncbi Virally encoded 7TM receptors
    M M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, Panum Institute, DK-2200, Denmark
    Oncogene 20:1582-93. 2001
    ..Thus, this and other virally encoded 7TM receptors appear to be attractive future drug targets...
  14. pmc Tumorigenesis induced by the HHV8-encoded chemokine receptor requires ligand modulation of high constitutive activity
    P J Holst
    Laboratory for Molecular Pharmacology, Department of Pharmacology, Panum Institute, University of Copenhagen, Copenhagen, Denmark
    J Clin Invest 108:1789-96. 2001
    ..These results indicate that induction of the KS-like disease in transgenic mice by ORF74 requires not only high constitutive signaling activity but also modulation of this activity by endogenous chemokines...
  15. ncbi The carboxyl terminus of human cytomegalovirus-encoded 7 transmembrane receptor US28 camouflages agonism by mediating constitutive endocytosis
    Maria Waldhoer
    Laboratory for Molecular Pharmacology, Panum Institute, University of Copenhagen, Copenhagen DK 2200, Denmark
    J Biol Chem 278:19473-82. 2003
    ..This demonstrates for the first time that the endocytic properties of a 7TM receptor can camouflage the agonist properties of a ligand...
  16. pmc Reversed binding of a small molecule ligand in homologous chemokine receptors - differential role of extracellular loop 2
    P C Jensen
    Department of Neuroscience and Pharmacology, Copenhagen University, Copenhagen, Denmark
    Br J Pharmacol 166:258-75. 2012
    ..Here we describe a novel piperidine-based compound with structural similarity to previously described CCR8-specific agonists, but containing a unique phenyl-tetrazol moiety which, in addition to activity at CCR8 was also active at CCR1...
  17. pmc Distinct expression and ligand-binding profiles of two constitutively active GPR17 splice variants
    T Benned-Jensen
    Department of Neuroscience and Pharmacology, The Panum Institute, Copenhagen University, Denmark
    Br J Pharmacol 159:1092-105. 2010
    ..Hence, we investigated gene expression and ligand-binding profiles of both splice variants and furthermore uncovered and characterized constitutive activity of both isoforms...
  18. ncbi Targeting CXCR4 in HIV cell-entry inhibition
    A Steen
    Department of Neuroscience and Pharmacology, Faculty of Health Sciences, Copenhagen University, Copenhagen, Denmark
    Mini Rev Med Chem 9:1605-21. 2009
    ....
  19. ncbi Identification of a novel site within G protein alpha subunits important for specificity of receptor-G protein interaction
    Arne Heydorn
    Laboratory for Molecular Pharmacology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
    Mol Pharmacol 66:250-9. 2004
    ....
  20. ncbi Similar activation of signal transduction pathways by the herpesvirus-encoded chemokine receptors US28 and ORF74
    Katherine A McLean
    Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute, University of Copenhagen, 2200 Copenhagen N, Denmark
    Virology 325:241-51. 2004
    ..As ORF74 is a known inducer of neoplasia, these findings may have important implications for cytomegalovirus-associated pathogenicity...
  21. ncbi The role of transmembrane segment II in 7TM receptor activation
    T Benned-Jensen
    Institute for Neuroscience and Pharmacology, The Panum Institute, Copenhagen University, Copenhagen N, Denmark
    Curr Mol Pharmacol 2:140-8. 2009
    ....
  22. ncbi Agonists and inverse agonists for the herpesvirus 8-encoded constitutively active seven-transmembrane oncogene product, ORF-74
    M M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, Panum Institute, University of Copenhagen, DK 2200 Copenhagen, Denmark
    J Biol Chem 274:956-61. 1999
    ..ORF-74 could serve as a target for the development of non-peptide inverse agonist drugs as demonstrated by the effect of Zn2+ on the metal ion site-engineered receptor...
  23. ncbi Kaposi sarcoma-associated herpes virus targets the lymphotactin receptor with both a broad spectrum antagonist vCCL2 and a highly selective and potent agonist vCCL3
    Hans R Lüttichau
    Laboratory for Molecular Pharmacology, Panum Institute, 18 6, Blegdamsvej 3, DK 2200 Copenhagen N, Denmark
    J Biol Chem 282:17794-805. 2007
    ....
  24. ncbi Molecular interaction of a potent nonpeptide agonist with the chemokine receptor CCR8
    Pia C Jensen
    Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute, Copenhagen University, Blegdamsvej 2, 2200 Copenhagen, Denmark
    Mol Pharmacol 72:327-40. 2007
    ....
  25. ncbi Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor
    Randi Ugleholdt
    Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK 2200 Copenhagen N, Denmark
    J Biol Chem 281:11050-7. 2006
    ....
  26. ncbi Molecular mechanism of 7TM receptor activation--a global toggle switch model
    Thue W Schwartz
    Laboratory for Molecular Pharmacology, The Panum Institute, University of Copenhagen, and 7TM Pharma A S, Hørsholm, Denmark
    Annu Rev Pharmacol Toxicol 46:481-519. 2006
    ....
  27. doi Ligand binding and micro-switches in 7TM receptor structures
    Rie Nygaard
    Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, DK 2200, Denmark
    Trends Pharmacol Sci 30:249-59. 2009
    ..e. especially TM-VI), which performs the large, global toggle switch movements connecting ligand binding with intracellular signaling...
  28. doi Chapter 8. Activation mechanisms of chemokine receptors
    Pia C Jensen
    Department of Neuroscience and Pharmacology, Laboratory for Molecular Pharmacology, The PanumInstitute, University of Copenhagen, Copenhagen, Denmark
    Methods Enzymol 461:171-90. 2009
    ..This also brings up the interesting discussion of allosterism, because small molecules in the chemokine field often interact with allosteric receptor sites...
  29. ncbi The CXC chemokine receptor encoded by herpesvirus saimiri, ECRF3, shows ligand-regulated signaling through Gi, Gq, and G12/13 proteins but constitutive signaling only through Gi and G12/13 proteins
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, Panum Institute, University of Copenhagen, 2200 Copenhagen N, Denmark
    J Biol Chem 279:32524-33. 2004
    ..The results suggest that the unique ligand selectivity of ECRF3 among ORF74 receptors could reflect differences in the cellular tropism of the gamma(2)-herpesviruses...
  30. doi Gating function of isoleucine-116 in TM-3 (position III:16/3.40) for the activity state of the CC-chemokine receptor 5 (CCR5)
    A Steen
    Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
    Br J Pharmacol 171:1566-79. 2014
    ..However, in 37% of chemokine receptors - a subgroup of 7TM receptors - it is a leucine indicating an altered function. Here, we describe the significance of this position and its possible interaction with TM-3 for CCR5 activity...
  31. ncbi Positive versus negative modulation of different endogenous chemokines for CC-chemokine receptor 1 by small molecule agonists through allosteric versus orthosteric binding
    Pia C Jensen
    Department of Neuroscience and Pharmacology, Copenhagen University, Blegdamsvej 3, DK 2200, Copenhagen, Denmark
    J Biol Chem 283:23121-8. 2008
    ....
  32. ncbi Exendin-4, but not dipeptidyl peptidase IV inhibition, increases small intestinal mass in GK rats
    Lotte Simonsen
    Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Blegdamsvej 3, DK 2200 Copenhagen N, Denmark
    Am J Physiol Gastrointest Liver Physiol 293:G288-95. 2007
    ..In conclusion, the continued presence of Ex-4 is necessary to maintain weight loss in GK rats. Effective antihyperglycemic treatment with Ex-4 increases intestinal mass reversibly, whereas DPPIV-I lacks intestinal effects...
  33. ncbi Microbiological exploitation of the chemokine system
    Peter J Holst
    Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute, University of Copenhagen, Denmark
    Microbes Infect 5:179-87. 2003
    ....
  34. ncbi High content screening for G protein-coupled receptors using cell-based protein translocation assays
    Charlotta Granas
    BioImage A S, Copenhagen, Denmark
    Comb Chem High Throughput Screen 8:301-9. 2005
    ....
  35. ncbi Virally encoded chemokines and chemokine receptors in the role of viral infections
    Peter J Holst
    Laboratory for Molecular Pharmacology, Department of Pharmacology, Panum Institute, Copenhagen, Denmark
    Contrib Microbiol 10:232-52. 2003
    ..These have already had their potential demonstrated in animal models and may in their native or modified forms represent useful therapies in humans...
  36. ncbi GIP-(3-42) does not antagonize insulinotropic effects of GIP at physiological concentrations
    Carolyn F Deacon
    Dept of Medical Physiology, The Panum Institute, Blegdamsvej 3, DK 2200 Copenhagen N, Denmark
    Am J Physiol Endocrinol Metab 291:E468-75. 2006
    ..We conclude that, although GIP-(3-42) can weakly antagonize cAMP accumulation and insulin output in vitro, it does not behave as a physiological antagonist in vivo...
  37. ncbi Activation of the CXCR3 chemokine receptor through anchoring of a small molecule chelator ligand between TM-III, -IV, and -VI
    Mette M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, University of Copenhagen, Blegdamsvej 3b, DK 2200, Copenhagen, Denmark
    Mol Pharmacol 71:930-41. 2007
    ..It is proposed that in rhodopsin-like 7TM receptors, small-molecule compounds in general act as agonists in a similar manner as here demonstrated with the artificial, metal ion site anchored chelators, by holding TM-VI bent inward...
  38. pmc The CCR5 receptor acts as an alloantigen in CCR5Delta32 homozygous individuals: identification of chemokineand HIV-1-blocking human antibodies
    H J Ditzel
    Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, DK 2200 Copenhagen, Denmark
    Proc Natl Acad Sci U S A 95:5241-5. 1998
    ..The identified human antibodies to CCR5 define an alloantigen that may cause allograft rejection in a mismatch situation even in individuals with no history of blood transfusions or i.v. drug abuse...
  39. pmc Structure, function and physiological consequences of virally encoded chemokine seven transmembrane receptors
    M M Rosenkilde
    Laboratory for Molecular Pharmacology, Department of Pharmacology, University of Copenhagen, Copenhagen, Denmark
    Br J Pharmacol 153:S154-66. 2008
    ..Finally, we highlight the emerging impact of these receptor on virus-mediated diseases...
  40. doi Porcine glucagon-like peptide-2: structure, signaling, metabolism and effects
    Nis B Pedersen
    Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
    Regul Pept 146:310-20. 2008
    ..In conclusion, pGLP-2 and hGLP-2 have similar effects in vivo and in vitro in spite of the structural differences. However, pGLP-2 is cleared more rapidly in pigs than hGLP-2...
  41. ncbi A highly conserved glycine within linker I and the extreme C terminus of G protein alpha subunits interact cooperatively in switching G protein-coupled receptor-to-effector specificity
    Evi Kostenis
    7TM Pharma, Fremtidsvej 3, 2970 Hoersholm, Denmark
    J Pharmacol Exp Ther 313:78-87. 2005
    ....
  42. ncbi AMD3465, a monomacrocyclic CXCR4 antagonist and potent HIV entry inhibitor
    Sigrid Hatse
    Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    Biochem Pharmacol 70:752-61. 2005
    ....
  43. pmc Functional analysis of the murine cytomegalovirus chemokine receptor homologue M33: ablation of constitutive signaling is associated with an attenuated phenotype in vivo
    Ruth Case
    Clinical Medical Virology Centre, University of Queensland, Sir Albert Sakzewski Virus Research Centre, Royal Children s Hospital, Herston 4029, Queensland, Australia
    J Virol 82:1884-98. 2008
    ..In addition, HCMV UL33 was found to partially compensate for the lack of M33 in vivo, suggesting conserved biological roles of the UL33 gene family...
  44. ncbi Mutations at the CXCR4 interaction sites for AMD3100 influence anti-CXCR4 antibody binding and HIV-1 entry
    Sigrid Hatse
    Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    FEBS Lett 546:300-6. 2003
    ..3. Thus, resistance of HIV-1 NL4.3 to AMD3100 is associated with a decreased dependence of the viral gp120 on Asp(262) of CXCR4, pointing to a different mode of interaction of wild-type versus AMD3100-resistant virus with CXCR4...
  45. pmc Modest human immunodeficiency virus coreceptor function of CXCR3 is strongly enhanced by mimicking the CXCR4 ligand binding pocket in the CXCR3 receptor
    Sigrid Hatse
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    J Virol 81:3632-9. 2007
    ..Moreover, the CXCR4 antagonist AMD3100 exhibited antagonistic and anti-HIV activities in U87.CD4.CXCR3[K300A, S304E] cells but not in U87.CD4.CXCR3[WT] cells...
  46. pmc Epstein-Barr virus-encoded BILF1 is a constitutively active G protein-coupled receptor
    Sarah J Paulsen
    Clinical Research Unit, Copenhagen University Hospital, Hvidovre, Denmark
    J Virol 79:536-46. 2005
    ..We suggest that EBV may use BILF1 to regulate Galphai-activated pathways during viral lytic replication, thereby affecting disease progression...