Development of low molecular weight HIV-1 protease dimerization inhibitors

Journal of Medicinal Chemistry

Volumn 48, Issue 6, 2005, Pages 2239-2242

  You, Seok Hwang ^a   Chmielewski, Jean ^a  

^a PURDUE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEINASE; PROTEINASE INHIBITOR;

ARTICLE; DIMERIZATION; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME ASSAY; ENZYME INHIBITION; HUMAN IMMUNODEFICIENCY VIRUS 1; MOLECULAR WEIGHT; PHARMACOPHORE; PROTEIN CROSS LINKING; VIRUS REPLICATION;

COMBINATORIAL CHEMISTRY TECHNIQUES; CROSS-LINKING REAGENTS; DIMERIZATION; HIV PROTEASE; HIV PROTEASE INHIBITORS; MODELS, MOLECULAR; MOLECULAR WEIGHT; MUTATION; OLIGOPEPTIDES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 15444380612     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm049581j     Document Type: Article

References (14)

1. Stites, W. Protein-protein interactions: interface structure, binding thermodynamis, and mutational analysis. Chem. Rev. 1997, 97, 1233-1250.
2. Thornton, J. S. Principles of protein-protein interactions. Proc. Natl. Acad. Sci. U.S.A. 1988, 93, 13-20.
3. Zutshi, R.; Brickner, M.; Chmielewski, J. Inhibiting the Asembly of Protein-Protein Interfaces. Curr. Opin. Chem. Biol. 1998, 2, 62-66.
4. Wlodawer, A.; Miller, A.; Jaskolski, M.; Sathyanarayana, B.; Baldwin, E.; Weber, I.; Selk, L.; Clawson, L.; Schneider, J.; Kent, S. Conserved Folding in Retroviral Proteases Crystal Structure of a Synthetic HIV-1 Protease. Science 1989, 245, 616-621.
5. Little, S.; Holte, S.; Routy, J.-P.; Daar, E.; Markowitz, M.; Collier, A.; Koup, R.; Mellors, J.; Connick, E.; Conway, B.; Kilby, M.; Wang, L.; Whitmomb, J.; Hellmann, N.; Richman, D. Antiretroviral-Drug Resistance among Patients Recently Infected with HIV. New. Eng. J. Med. 2002, 347, 385-394.
6. Flexner, C. HIV-Protease Inhibitors. N. Engl. J. Med. 1998, 338, 1281-1292.
7. Gustchina, A,; Weber, I. T. Comparative Analysis of the Sequences and Structures of HIV-1 and HIV-2 Proteases. Proteins: Struct., Funct., Genet. 1991, 10, 325-329.
8. Shultz, M. D.; Bowman, M. J.; Ham, Y.-W.; Zhao, X.; Tora, G.; Chmielewski, J. Small-Molecule Inhibitors of HIV-1 Protease Dimerization Derived from Cross-Linked Interfacial Peptides. Angew. Chem., Int. Ed. 2000, 39, 2710-2713.
9. Bowman, M. J.; Chmielewski, J. Novel strategies for targeting the dimerization interface of HIV protease with cross-linked interfacial peptides. Biopolym.: Pept. Sci. 2002, 66, 126-133.
10. Zutshi, R.; Franciskovich, J.; Shultz, M.; Schweitzer, B.; Bishop, P.; Wilson, M.; Chmielewski, J. Targeting the Dimerization Interface of HIV-1 Protease: Inhibition with Crosslinked Interfacial Peptides. J. Am. Chem. Soc. 1997, 119, 4841-4845.
11. Shultz, M. D.; Ham, Y.-W.; Lee, S.-G.; Davis, D.; Brown, C.; Chmielewski, J. Small Molecule Dimerization inhibitors of HIV Protease: A Focused Library Approach. J. Am. Chem. Soc. 2004, 126, 9886-9887.
12. Rink, H. Solid-Phase Synthesis of Protected Peptide Fragments Using a Trialkyloxy-Diphenyl-Methyl Ester Resin. Tetrahedron Lett. 1987, 28, 3787-3790.
13. Toth, M. V.; Marshall, G. R. A Simple, Continuous Fluorometric Assay for HIV Protease. Int. J. Pept. Protein Res. 1990, 36, 544-550.
14. Zhang, Z. Y.; Poorman, R. A.; Maggiora, L. L.; Heinrikson, R. L.; Kezdy, F. J. Dissociative Inhibition of Dimeric Enzymes: Kinetic Characterization of the Inhibition of HIV-1 Protease by Its COOH-Terminal Tetrapeptide. J. Biol. Chem. 1991, 266, 15591-15594.