Crystallographic analysis of the binding modes of thiazoloisoindolinone non-nucleoside inhibitors to HIV-1 reverse transcriptase and comparison with modeling studies

Journal of Medicinal Chemistry

Volumn 42, Issue 19, 1999, Pages 3845-3851

  Ren, Jingshan ^a   Esnouf, Robert M ^a,b   Hopkins, Andrew L ^a   Stuart, David I ^a,b   Stammers, David K ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

5(9BH) 9B PHENYL 2,3 DIHYDROTHIAZOLO[2,3 A]ISOINDOL3 3 CARBOXYLIC ACID METHYL ESTER; 9B (3 METHYLPHENYL) 2,3 DIHYDROTHIAZOLO[2,3 A]ISOINDOL 5(9BH) ONE; DELAVIRDINE; DIDANOSINE; EFAVIRENZ; LAMIVUDINE; NEVIRAPINE; RNA DIRECTED DNA POLYMERASE INHIBITOR; STAVUDINE; THIAZOLOISOINDOLINONE DERIVATIVE; UNCLASSIFIED DRUG; ZALCITABINE; ZIDOVUDINE;

ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; ENZYME INHIBITOR INTERACTION; HUMAN IMMUNODEFICIENCY VIRUS 1; MOLECULAR INTERACTION; NONHUMAN; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

CRYSTALLOGRAPHY, X-RAY; HIV-1 REVERSE TRANSCRIPTASE; INDOLES; MODELS, CHEMICAL; MODELS, MOLECULAR; PROTEIN BINDING; PROTEIN CONFORMATION; REVERSE TRANSCRIPTASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES;

EID: 0033598368     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990275t     Document Type: Article

References (24)

1. De Clercq, E. The role of nonnucleoside reverse transcriptase inhibitors (NNRTIs) in the therapy of HIV-1 infection. Antiviral Res. 1998, 38, 153-179.
2. Kohlstaedt, L. A.; Wang, J.; Friedman, J. M.; Rice, P. A.; Steitz, T. A. Crystal structure at 3.5 Å resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 1992, 256, 1783-1790.
3. Ren, J.; Esnouf, R.; Garman, E.; Somers, D.; Ross, C.; Kirby, I.; Keeling, J.; Darby, G.; Jones, Y.; Stuart, D.; Stammers, D. High-resolution structures of HIV-1 RT from four RT-inhibitor complexes. Nature Struct. Biol. 1995, 2, 293-302.
4. Ding, J.; Das, K.; Tantillo, C.; Zhang, W.; Clark, A. D. J.; Jessen, S.; Lu, X.; Hsiou, Y.; Jacobo-Molina, A.; Andries, K.; Pauwels, R.; Moereels, H.; Koymans, L.; Janssen, P. A. J.; Smith, R. H. J.; Kroeger Koepke, R.; Michejda, C. J.; Hughes, S. H.; Arnold, E. Structure of HIV-1 reverse transcriptase in a complex with the nonnucleoside inhibitor α-APA R 95845 at 2.8 Å resolution. Structure 1995, 3, 365-379.
5. Esnouf, R.; Ren, J.; Ross, C.; Jones, Y.; Stammers, D.; Stuart, D. Mechanism of inhibition of HIV-1 reverse transcriptase by nonnucleoside inhibitors. Nature Struct. Biol. 1995, 2, 303-308.
6. Ren, J.; Esnouf, R.; Hopkins, A.; Ross, C.; Jones, Y.; Stammers, D.; Stuart, D. The structure of HIV-1 reverse transcriptase complexed with 9-chloro-TIBO: lessons for inhibitor design. Structure 1995, 3, 915-926.
7. Hopkins, A. L.; Ren, J.; Esnouf, R. M.; Willcox, B. E.; Jones, E. Y.; Ross, C.; Miyasaka, T.; Walker, R. T.; Tanaka, H.; Stammers, D. K.; Stuart, D. I. Complexes of HIV-1 reverse transcriptase with inhibitors of the HEPT series reveal conformational changes relevant to the design of potent nonnucleoside inhibitors. J. Med. Chem. 1996, 39, 1589-1600.
8. Esnouf, R. M.; Ren, J.; Hopkins, A. L.; Ross, C. K.; Jones, E. Y.; Stammers, D. K.; Stuart, D. I. Unique features in the structure of the complex between HIV-1 reverse transcriptase and the bis-(heteroaryl)piperazine (BHAP) U-90152 explain resistance mutations for this nonnucleoside inhibitor. Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 3984-3989.
9. Ren, J.; Esnouf, R. M.; Hopkins, A. L.; Warren, J.; Balzarini, J.; Stuart, D. I.; Stammers, D. K. Crystal structures of HIV-1 reverse transcriptase in complex with carboxanilide derivatives. Biochemistry 1998, 37, 14394-14403.
10. Richman, D.; Shih, C.-K.; Lowy, I.; Rose, J.; Prodanovich, P.; Goff, S.; Griffin, J. Human immunodeficiency virus type 1 mutants resistant to nonnucleoside inhibitors of reverse transcriptase arise in tissue culture. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 11241-11245.
11. Richman, D. D.; Havlir, D.; Corbeil, J.; Looney, D.; Ignacio, C.; Spector, S. A.; Sullivan, J.; Cheeseman, S.; Barringer, K.; Pauletti, D.; Shih, C.-K.; Myers, M.; Griffin, J. Nevirapine resistance mutations of human immunodeficiency virus type 1 selected during therapy. J. Virol. 1994, 68, 1660-1666.
12. Esnouf, R. M.; Stuart, D. I.; De Clercq, E.; Schwartz, E.; Balzarini, J. Models which explain the inhibition of reverse transcriptase by HIV-1-specific (thio)carboxanilide derivatives. Biochem. Biophys. Res. Commun. 1997, 234, 458-464.
13. Yang, S. S.; Pattabiraman, N.; Gussio, R.; Pallansch, L.; Buckheit, R. W. J.; Bader, J. P. Cross-resistance analysis and molecular modeling of nonnucleoside reverse transcriptase inhibitors targeting drug-resistance mutations in the reverse transcriptase of human immunodeficiency virus. Leukemia 1997, 11, 89-92.
14. Mertens, A.; Zilch, H.; Konig, B.; Schafer, W.; Poll, T.; Kampe, W.; Seidel, H.; Leser, U.; Leinert, H. Selective nonnucleoside HIV-1 reverse transcriptase inhibitors. New 2,3-dihydrothiazolo-[2,3-a]-isoindol-5(9bH)-ones and related compounds with anti-HIV-1 activity. J. Med. Chem. 1993, 36, 2526-2535.
15. Maass, G.; Immendoerfer, U.; Koenig, B.; Leser, U.; Mueller, B.; Goody, R.; Pfaff, E. Viral resistance to the thiazolo-iso-indolin-ones, a new class of nonnucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. Antimicrob. Agents Chemother. 1993, 37, 2612-2617.
16. Schafer, W.; Friebe, W.-G.; Leinert, H.; Mertens, A.; Poll, T.; von der Saal, W.; Zilch, H.; Ziegler, M. L. Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase: Molecular Modelling and X-ray Structure Investigations. J. Med. Chem. 1993, 36, 726-732.
17. Mui, P. W.; Jacober, S. P.; Hargrave, K. D.; Adams, J. Crystal structure of nevirapine, a nonnucleoside inhibitor of HIV-1 reverse transcriptase, and computational alignment with a structurally diverse inhibitor. J. Med. Chem. 1992, 35, 201-202.
18. Schinazi, R. F.; Larder, B. A.; Mellors, J. W. Mutations in retroviral genes associated with drug resistance. Int. Antiviral News 1997, 5, 129-135.
19. Stammers, D. K.; Somers, D. O. N.; Ross, C. K.; Kirby, I.; Ray, P. H.; Wilson, J. E.; Norman, M.; Ren, J. S.; Esnouf, R. M.; Garman, E. F.; Jones, E. Y.; Stuart, D. I. Crystals of HIV-1 reverse transcriptase diffracting to 2.2 Å resolution. J. Mol. Biol. 1994, 242, 586-588.
20. Otwinowski, Z.; Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 1996, 276, 307-326.
21. Esnouf, R. M.; Ren, J.; Garman, E. F.; Somers, D. O. N.; Ross, C. K.; Jones, E. Y.; Stammers, D. K.; Stuart, D. I. Continuous and discontinuous changes in the unit cell of HIV-1 reverse transcriptase crystals on dehydration. Acta Crystallogr. 1998, D54, 938-954.
22. Brunger, A. T. X-PLOR Manual; Yale University Press: New Haven, CT, 1992.
23. Brunger, A. T.; Adams, P. D.; Clore, G. M.; Delano, W. L.; Gros, P.; Grosse, K. R. W.; Jiang, J. S.; Kuszewski, J.; Nilges, M.; Pannu, N. S.; Read, R. J.; Rice, L. M.; Simonson, T.; Warren, G. L. Crystallography and NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr. 1998, D54, 905-921.
24. Jones, T. A. Interactive computer graphics: FRODO. Methods Enzymol. 1985, 115, 157-171.