Marc C Nicklaus

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. ncbi request reprint Model of full-length HIV-1 integrase complexed with viral DNA as template for anti-HIV drug design
    Rajeshri G Karki
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Frederick, MD 21702, USA
    J Comput Aided Mol Des 18:739-60. 2004
  2. pmc Combining docking with pharmacophore filtering for improved virtual screening
    Megan L Peach
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA
    J Cheminform 1:6. 2009
  3. pmc Application of azide-alkyne cycloaddition 'click chemistry' for the synthesis of Grb2 SH2 domain-binding macrocycles
    Won Jun Choi
    Laboratory of Medicinal Chemistry, CCR, NCI, NIH, Frederick, MD 21702, USA
    Bioorg Med Chem Lett 16:5265-9. 2006
  4. ncbi request reprint Evaluation of macrocyclic Grb2 SH2 domain-binding peptide mimetics prepared by ring-closing metathesis of C-terminal allylglycines with an N-terminal beta-vinyl-substituted phosphotyrosyl mimetic
    Shinya Oishi
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Institutes of Health, PO Box B, Bldg 376 Boyles St Frederick, MD 21702 1201, USA
    Bioorg Med Chem 13:2431-8. 2005
  5. ncbi request reprint Utilization of a nitrobenzoxadiazole (NBD) fluorophore in the design of a Grb2 SH2 domain-binding peptide mimetic
    Zhen Dan Shi
    Laboratory of Medicinal Chemistry, CCR, NCI, NIH, Frederick, MD 21702, USA
    Bioorg Med Chem Lett 15:1385-8. 2005
  6. ncbi request reprint Conformationally constrained analogues of diacylglycerol (DAG). 23. Hydrophobic ligand-protein interactions versus ligand-lipid interactions of DAG-lactones with protein kinase C (PK-C)
    Hirokazu Tamamura
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute Frederick, National Institutes of Health, Building 376, Room 104, Frederick, Maryland 21702, USA
    J Med Chem 47:4858-64. 2004
  7. ncbi request reprint Examination of acylated 4-aminopiperidine-4-carboxylic acid residues in the phosphotyrosyl+1 position of Grb2 SH2 domain-binding tripeptides
    Sang Uk Kang
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702 1201, USA
    J Med Chem 50:1978-82. 2007
  8. pmc Conformationally constrained analogues of diacylglycerol (DAG). 25. Exploration of the sn-1 and sn-2 carbonyl functionality reveals the essential role of the sn-1 carbonyl at the lipid interface in the binding of DAG-lactones to protein kinase C
    Ji Hye Kang
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
    J Med Chem 48:5738-48. 2005
  9. ncbi request reprint Sculpting the bicyclo[3.1.0]hexane template of carbocyclic nucleosides to improve recognition by herpes thymidine kinase
    Maria J Comin
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, 376 Boyles Street, Frederick, Maryland 21702, USA
    J Am Chem Soc 129:6216-22. 2007
  10. doi request reprint PDB ligand conformational energies calculated quantum-mechanically
    Markus Sitzmann
    Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, NCI Frederick, 376 Boyles Street, Frederick, Maryland 21702, USA
    J Chem Inf Model 52:739-56. 2012

Collaborators

Detail Information

Publications41

  1. ncbi request reprint Model of full-length HIV-1 integrase complexed with viral DNA as template for anti-HIV drug design
    Rajeshri G Karki
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Frederick, MD 21702, USA
    J Comput Aided Mol Des 18:739-60. 2004
    ..The results indicate that the diketo-acid IN inhibitors probably chelate the metal ion in the catalytic site and also prevent the exposure of the 3'-processed end of the viral DNA to human DNA...
  2. pmc Combining docking with pharmacophore filtering for improved virtual screening
    Megan L Peach
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA
    J Cheminform 1:6. 2009
    ..However, the scoring functions that are used with docking are typically not successful at correctly ranking ligands according to binding affinity or even distinguishing correct poses of a given ligand from incorrect ones...
  3. pmc Application of azide-alkyne cycloaddition 'click chemistry' for the synthesis of Grb2 SH2 domain-binding macrocycles
    Won Jun Choi
    Laboratory of Medicinal Chemistry, CCR, NCI, NIH, Frederick, MD 21702, USA
    Bioorg Med Chem Lett 16:5265-9. 2006
    ..The open-chain dimer was also found to have affinity equal to the dimeric macrocycle. This work represents the first application of 'click chemistry' to the synthesis of SH2 domain-binding inhibitors and indicates its potential utility...
  4. ncbi request reprint Evaluation of macrocyclic Grb2 SH2 domain-binding peptide mimetics prepared by ring-closing metathesis of C-terminal allylglycines with an N-terminal beta-vinyl-substituted phosphotyrosyl mimetic
    Shinya Oishi
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Institutes of Health, PO Box B, Bldg 376 Boyles St Frederick, MD 21702 1201, USA
    Bioorg Med Chem 13:2431-8. 2005
    ..An understanding of the conformational consequences of such i to i+3 ring closure may facilitate its application to other systems where bend geometries are desired...
  5. ncbi request reprint Utilization of a nitrobenzoxadiazole (NBD) fluorophore in the design of a Grb2 SH2 domain-binding peptide mimetic
    Zhen Dan Shi
    Laboratory of Medicinal Chemistry, CCR, NCI, NIH, Frederick, MD 21702, USA
    Bioorg Med Chem Lett 15:1385-8. 2005
    ..This novel agent should serve as a useful tool to visualize the actions of this class of Grb2 SH2 domain-binding antagonists in whole cell systems...
  6. ncbi request reprint Conformationally constrained analogues of diacylglycerol (DAG). 23. Hydrophobic ligand-protein interactions versus ligand-lipid interactions of DAG-lactones with protein kinase C (PK-C)
    Hirokazu Tamamura
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute Frederick, National Institutes of Health, Building 376, Room 104, Frederick, Maryland 21702, USA
    J Med Chem 47:4858-64. 2004
    ....
  7. ncbi request reprint Examination of acylated 4-aminopiperidine-4-carboxylic acid residues in the phosphotyrosyl+1 position of Grb2 SH2 domain-binding tripeptides
    Sang Uk Kang
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702 1201, USA
    J Med Chem 50:1978-82. 2007
    ..The highest affinities were obtained using phenylethyl carbamate and phenylbutyrylamide functionalities...
  8. pmc Conformationally constrained analogues of diacylglycerol (DAG). 25. Exploration of the sn-1 and sn-2 carbonyl functionality reveals the essential role of the sn-1 carbonyl at the lipid interface in the binding of DAG-lactones to protein kinase C
    Ji Hye Kang
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
    J Med Chem 48:5738-48. 2005
    ..The parent DAG-lactones, E-6 and Z-7, were designed to bind exclusively in the sn-2 binding mode to ensure the correct orientation and disposition of pharmacophores at the binding site...
  9. ncbi request reprint Sculpting the bicyclo[3.1.0]hexane template of carbocyclic nucleosides to improve recognition by herpes thymidine kinase
    Maria J Comin
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, 376 Boyles Street, Frederick, Maryland 21702, USA
    J Am Chem Soc 129:6216-22. 2007
    ..The bicyclo[3.1.0]hexane template represents a privileged rigid template for sculpting other carbocyclic nucleosides to meet the demands of specific receptors...
  10. doi request reprint PDB ligand conformational energies calculated quantum-mechanically
    Markus Sitzmann
    Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, NCI Frederick, 376 Boyles Street, Frederick, Maryland 21702, USA
    J Chem Inf Model 52:739-56. 2012
    ..Torsional sampling around the crystal conformation at the molecular mechanics level using the MMFF94s force field typically led to an increase in energy...
  11. ncbi request reprint Utilization of a common pathway for the synthesis of high affinity macrocyclic Grb2 SH2 domain-binding peptide mimetics that differ in the configuration at one ring junction
    Zhen Dan Shi
    Laboratory of Medicinal Chemistry, CCR, NCI, NIH, P O Box B, Bldg 376 Boyles St, Frederick, MD 21702 1201, USA
    Chem Biodivers 2:447-56. 2005
    ..Therefore, little affinity would be lost through a non-stereoselective synthesis of the C(14)-center. Further studies are in progress to explore reduced structural complexity at the C(14)-center...
  12. ncbi request reprint Metal-dependent inhibition of HIV-1 integrase by beta-diketo acids and resistance of the soluble double-mutant (F185K/C280S)
    Christophe Marchand
    Laboratory of Molecular Pharmacology, Center for Cancer Research, Bldg 37, Rm 5068, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4255, USA
    Mol Pharmacol 64:600-9. 2003
    ....
  13. pmc Directed discovery of agents targeting the Met tyrosine kinase domain by virtual screening
    Megan L Peach
    Basic Research Program, SAIC Frederick, Inc, NCI Frederick, Frederick, Maryland 21702, USA
    J Med Chem 52:943-51. 2009
    ..The predicted binding modes and target selectivity of these compounds are discussed and compared to other known Met TK inhibitors...
  14. ncbi request reprint Synthesis and conformational analysis of a locked analogue of carbovir built on a bicyclo[3.1.0]hex-2-enyl template
    Yongseok Choi
    Laboratory of Medicinal Chemistry, Center for Cancer Research, NCI Frederick, NIH, Frederick, Maryland 21702, USA
    Nucleosides Nucleotides Nucleic Acids 22:2077-91. 2003
    ..The bicyclo[3.1.0]hex-2-yl nucleosides 12 and 13 that were inactive against HIV exhibited stiffer resistance to having a planar, fused cyclopentane moiety...
  15. doi request reprint Computational tools and resources for metabolism-related property predictions. 2. Application to prediction of half-life time in human liver microsomes
    Alexey V Zakharov
    CADD Group, Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA
    Future Med Chem 4:1933-44. 2012
    ..We report on our efforts to develop QSAR models for metabolic stability of compounds, based on in vitro half-life assay data measured in human liver microsomes...
  16. ncbi request reprint Virtual screening application of a model of full-length HIV-1 integrase complexed with viral DNA
    Chenzhong Liao
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Frederick, MD 21702, USA
    Bioorg Med Chem Lett 17:5361-5. 2007
    ..Virtual screening methods including docking and filtering by predicted ADME/Tox properties yielded several microM level inhibitors of the strand transfer reaction catalyzed by wild-type HIV-1 integrase...
  17. pmc Identification of Shc Src homology 2 domain-binding peptoid-peptide hybrids
    Won Jun Choi
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Insitutes of Health, Frederick, Maryland 21702, USA
    J Med Chem 52:1612-8. 2009
    ..These results could provide a foundation for further structural optimization of Shc SH2 domain-binding peptide mimetics...
  18. pmc Comprehensive structural studies of 2',3'-difluorinated nucleosides: comparison of theory, solution, and solid state
    Joseph J Barchi
    Laboratory of Medicinal Chemistry, National Cancer Institute, Frederick, National Institutes of Health, 376 Boyles Street, P O Box B, Frederick, Maryland 21702, USA
    J Am Chem Soc 130:9048-57. 2008
    ..These data, along with previously reported data by us and others concerning monofluorinated nucleoside conformations, were used to propose a model of how fluorine influences different aspects of nucleoside conformations...
  19. pmc Polo-box domain: a versatile mediator of polo-like kinase function
    Jung Eun Park
    Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bldg 37, Rm 3118, Bethesda, MD, 20892 4258, USA
    Cell Mol Life Sci 67:1957-70. 2010
    ..In this review, current understanding of the structure and functions of PBD, mode of PBD-dependent interactions and substrate phosphorylation, and other phospho-independent functions of PBD are discussed...
  20. doi request reprint Inhibitors of human tyrosyl-DNA phospodiesterase (hTdp1) developed by virtual screening using ligand-based pharmacophores
    Iwona E Weidlich
    Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Frederick, MD 21702, USA
    Bioorg Med Chem 18:182-9. 2010
    ..94 microM. The obtained novel chemotype may provide a new scaffold for developing inhibitors of Tdp1...
  21. ncbi request reprint Design and synthesis of conformationally constrained Grb2 SH2 domain binding peptides employing alpha-methylphenylalanyl based phosphotyrosyl mimetics
    Shinya Oishi
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA
    J Med Chem 48:764-72. 2005
    ..Similar beta-macrocyclization may potentially be extended to SH2 domain systems other than Grb2, where bend geometries are required...
  22. pmc Tautomerism and magnesium chelation of HIV-1 integrase inhibitors: a theoretical study
    Chenzhong Liao
    Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, NCI Frederick, 376 Boyles St, Frederick, MD 21702, USA
    ChemMedChem 5:1053-66. 2010
    ..This supports the hypothesis that, in the binding site of IN after 3'-processing, the terminal 3'-OH of viral DNA interacts with one Mg(2+) by chelation...
  23. pmc Authentic HIV-1 integrase inhibitors
    Chenzhong Liao
    Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Frederick, MD 21702, USA
    Future Med Chem 2:1107-22. 2010
    ..Current and future attention will be focused on the development of novel authentic IN inhibitors with the goal of overcoming viral resistance...
  24. ncbi request reprint Prosit, an online service to calculate pseudorotational parameters of nucleosides and nucleotides
    Guangyu Sun
    Laboratory of Medicinal Chemistry, NCI Frederick, CCR, NCI, NIH, DHHS, Frederick, Maryland, USA
    Nucleosides Nucleotides Nucleic Acids 24:1029-32. 2005
    ..As examples, the sugar conformations in a parallel-stranded guanine tetraplex and a four-way Holliday junction are presented here...
  25. ncbi request reprint Structure, stability, and NMR properties of lower fullerenes C38-C50 and azafullerene C44N6
    Guangyu Sun
    Laboratory of Medicinal Chemistry, NCI Frederick, CCR, NCI, NIH, DHHS, 376 Boyles St, Frederick, Maryland 21702, USA
    J Phys Chem A 109:4617-22. 2005
    ..The (13)C NMR chemical shifts and nucleus-independent chemical shifts (NICS) for the stable isomers of each fullerene are presented...
  26. pmc Structural and functional analyses of minimal phosphopeptides targeting the polo-box domain of polo-like kinase 1
    Sang Moon Yun
    Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Nat Struct Mol Biol 16:876-82. 2009
    ..The mode of interaction between the minimal peptide and PBD may provide a template for designing therapeutic agents that target PLK1...
  27. ncbi request reprint Acylsulfonamide-containing PTP1B inhibitors designed to mimic an enzyme-bound water of hydration
    Ding Guo Liu
    Laboratory of Medicinal Chemistry, CCR, NCI, NIH, NCI Frederick, Frederick, MD 21702, USA
    Bioorg Med Chem Lett 13:3005-7. 2003
    ..In general, modest potency enhancements were observed. Arylacylsulfonamides represent a structure-based extension of inhibitor design that may have broader utility in the development of PTP1B inhibitors...
  28. pmc Computational tools and resources for metabolism-related property predictions. 1. Overview of publicly available (free and commercial) databases and software
    Megan L Peach
    Basic Science Program, SAIC Frederick, Inc CADD Group, Chemical Biology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA
    Future Med Chem 4:1907-32. 2012
    ..Our aim is to give a clear overview of the areas and aspects of metabolism prediction in which the currently available resources are useful and accurate, and the areas in which they are inadequate or missing entirely...
  29. ncbi request reprint Experimental and structural evidence that herpes 1 kinase and cellular DNA polymerase(s) discriminate on the basis of sugar pucker
    Victor E Marquez
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, 376 Boyles St, Frederick, MD, 21702, USA
    J Am Chem Soc 126:543-9. 2004
    ....
  30. pmc Software and resources for computational medicinal chemistry
    Chenzhong Liao
    Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Frederick, MD 21702, USA
    Future Med Chem 3:1057-85. 2011
    ..This article reviews software and other resources related to computer-aided drug design approaches, putting particular emphasis on structure-based drug design, ligand-based drug design, chemical databases and chemoinformatics tools...
  31. pmc Computer tools in the discovery of HIV-1 integrase inhibitors
    Chenzhong Liao
    Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, NCI Frederick, 376 Boyles Street, Frederick, MD 21702, USA
    Future Med Chem 2:1123-40. 2010
    ..Different structurally diverse integrase inhibitors have been identified by, or with significant help from, various CADD tools...
  32. pmc A new approach to radial basis function approximation and its application to QSAR
    Alexey V Zakharov
    CADD Group, Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, NCI Frederick, 376 Boyles St, Frederick, Maryland 21702, United States
    J Chem Inf Model 54:713-9. 2014
    ..Using our new method, we have created models for physicochemical and toxicity endpoints, which we have made freely available in the form of an online service at http://cactus.nci.nih.gov/chemical/apps/cap...
  33. pmc QSAR modeling of imbalanced high-throughput screening data in PubChem
    Alexey V Zakharov
    CADD Group, Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, NCI Frederick, 376 Boyles St, Frederick, Maryland 21702, United States
    J Chem Inf Model 54:705-12. 2014
    ..We also report on our efforts to incorporate the most predictive of our models in the publicly available NCI/CADD Group Web services ( http://cactus.nci.nih.gov/chemical/apps/cap)...
  34. pmc Optical structure recognition software to recover chemical information: OSRA, an open source solution
    Igor V Filippov
    Laboratory of Medicinal Chemistry, SAIC Frederick, Inc, NCI Frederick, Frederick, Maryland 21702, USA
    J Chem Inf Model 49:740-3. 2009
    ....
  35. ncbi request reprint Evidence that sequence homologous region in LRAT-like proteins possesses anti-proliferative activity and DNA binding properties: translational implications and mechanism of action
    Denise Perry Simmons
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Carcinogenesis 27:693-707. 2006
    ....
  36. ncbi request reprint Azido-containing aryl beta-diketo acid HIV-1 integrase inhibitors
    Xuechun Zhang
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Institutes of Health, MD, USA
    Bioorg Med Chem Lett 13:1215-9. 2003
    ..The ability of azido-containing inhibitors to exhibit potent inhibition of IN and antiviral protection in HIV-infected cells, renders the azide group of potential value in the further development of ADK-based IN inhibitors...
  37. ncbi request reprint PROSIT: pseudo-rotational online service and interactive tool, applied to a conformational survey of nucleosides and nucleotides
    Guangyu Sun
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, NIH, DHHS, NCI Frederick, 376 Boyles St, Frederick, Maryland 21702, USA
    J Chem Inf Comput Sci 44:1752-62. 2004
    ..We introduce the term "central conformation" to describe this part of the pseudorotational hyperspace in contrast to the conventional north and south conformations...
  38. pmc Tautomerism in large databases
    Markus Sitzmann
    Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, NCI Frederick, 376 Boyles St, Frederick, MD 21702, USA
    J Comput Aided Mol Des 24:521-51. 2010
    ..Projected onto the set of unique structures (by FICuS identifier), this still occurred in about 1.5% of the cases. Tautomeric overlap across all constituent databases in CSDB was found for nearly 10% of the records in the collection...
  39. pmc Inhibitors for the hepatitis C virus RNA polymerase explored by SAR with advanced machine learning methods
    Iwona E Weidlich
    Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA
    Bioorg Med Chem 21:3127-37. 2013
    ..We also identified NS5B inhibitors with two novel non-nucleoside chemical motifs...
  40. ncbi request reprint Differential binding modes of diacylglycerol (DAG) and DAG lactones to protein kinase C (PK-C)
    Dina M Sigano
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
    J Med Chem 46:1571-9. 2003
    ..As these analogous DAGs and DAG lactones have almost identical log P values, this difference in binding affinity is a direct result of the entropic advantage of constraining the glycerol backbone...
  41. doi request reprint Comparison of nine programs predicting pK(a) values of pharmaceutical substances
    Chenzhong Liao
    Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, NCI Frederick, 376 Boyles St, Frederick, Maryland 21702, USA
    J Chem Inf Model 49:2801-12. 2009
    ..5 was not as expected, with a mean absolute deviation of 1.283 and an r(2) value of 0.579, indicating the potential for further development of this type of approach to pK(a) prediction...