Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease

Journal of Medicinal Chemistry

Volumn 56, Issue 3, 2013, Pages 1074-1083

  Zhang, Hongmei ^a   Wang, Yuan Fang ^a   Shen, Chen Hsiang ^a   Agniswamy, Johnson ^a   Rao, Kalapala Venkateswara ^b   Xu, Chun Xiao ^b   Ghosh, Arun K ^b   Harrison, Robert W ^a   Weber, Irene T ^a  

^a GEORGIA STATE UNIVERSITY   (United States)

^b PURDUE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; ARGININE; ASPARAGINE; GLUTAMINE; GLYCINE; GRL 0519; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE; OXYGEN; TETRAHYDROFURAN DERIVATIVE; UNCLASSIFIED DRUG; VALINE;

AMINO ACID SUBSTITUTION; ANTIVIRAL ACTIVITY; ARTICLE; BINDING AFFINITY; CATALYSIS; CHEMICAL INTERACTION; CONFORMATION; CRYSTAL STRUCTURE; DRUG BINDING SITE; DRUG EFFICACY; DRUG STRUCTURE; ENZYME INHIBITION; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HYDROGEN BOND; HYDROPHOBICITY; NONHUMAN; PROTEIN EXPRESSION; VIRUS MUTANT;

ANTI-HIV AGENTS; CRYSTALLOGRAPHY, X-RAY; FURANS; HIV PROTEASE; MODELS, MOLECULAR; MUTATION; SULFONAMIDES;

EID: 84873893231     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm301519z     Document Type: Article

References (41)

1. UNAIDS Report on the Global AIDS Epidemic; UNAIDS: Geneva, 2010.
2. Girard, M. P.; Bansal, G. P. HIV/AIDS vaccines: a need for new concepts? Int. Rev. Immunol. 2008, 27, 447-471
3. Brenner, B. G.; Turner, D.; Wainberg, M. A. HIV-1 drug resistance: can we overcome? Expert Opin. Biol. Ther. 2002, 2, 751-761
4. Darke, P. L.; Nutt, R. F.; Brady, S. F.; Garsky, V. M.; Ciccarone, T. M.; Leu, C. T.; Lumma, P. K.; Freidinger, R. M.; Veber, D. F.; Sigal, I. S. HIV-1 protease specificity of peptide cleavage is sufficient for processing of gag and pol polyproteins Biochem. Biophys. Res. Commun. 1988, 156, 297-303
5. Oroszlan, S.; Luftig, R. B. Retroviral proteinases Curr. Top. Microbiol. Immunol. 1990, 157, 153-185
6. Richman, D. D.; Morton, S. C.; Wrin, T.; Hellmann, N.; Berry, S.; Shapiro, M. F.; Bozzette, S. A. The prevalence of antiretroviral drug resistance in the United States AIDS 2004, 18, 1393-1401
7. Weber, I. T.; Agniswamy, J. HIV-1 Protease: Structural Perspectives on Drug Resistance Viruses (Basel) 2009, 1, 1110-1136
8. Weber, I. T.; Wang, Y.-F. HIV-1 Protease: Role in Viral Replication, Protein-Ligand X-Ray Crystal Structures and Inhibitor Design. In Aspartic Acid Proteases as Therapeutic Targets; Wiley-VCH: New York, 2010; pp 107-137.
9. Miller, V. International perspectives on antiretroviral resistance. Resistance to protease inhibitors JAIDS, J. Acquired Immune Defic. Syndr. 2001, 26 (Suppl 1) S34-S50
10. Ghosh, A. K.; Kincaid, J. F.; Cho, W.; Walters, D. E.; Krishnan, K.; Hussain, K. A.; Koo, Y.; Cho, H.; Rudall, C.; Holland, L.; Buthod, J. Potent HIV protease inhibitors incorporating high-affinity P2-ligands and (R)-(hydroxyethylamino)sulfonamide isostere Bioorg. Med. Chem. Lett. 1998, 8, 687-690
11. Surleraux, D. L.; Tahri, A.; Verschueren, W. G.; Pille, G. M.; de Kock, H. A.; Jonckers, T. H.; Peeters, A.; De Meyer, S.; Azijn, H.; Pauwels, R.; de Bethune, M. P.; King, N. M.; Prabu-Jeyabalan, M.; Schiffer, C. A.; Wigerinck, P. B. Discovery and selection of TMC114, a next generation HIV-1 protease inhibitor J. Med. Chem. 2005, 48, 1813-1822
12. Ghosh, A. K.; Xu, C. X.; Rao, K. V.; Baldridge, A.; Agniswamy, J.; Wang, Y. F.; Weber, I. T.; Aoki, M.; Miguel, S. G.; Amano, M.; Mitsuya, H. Probing multidrug-resistance and protein-ligand interactions with oxatricyclic designed ligands in HIV-1 protease inhibitors ChemMedChem 2010, 5, 1850-1854
13. Johnson, V. A.; Calvez, V.; Gunthard, H. F.; Paredes, R.; Pillay, D.; Shafer, R.; Wensing, A. M.; Richman, D. D. 2011 update of the drug resistance mutations in HIV-1 Top. Antiviral Med. 2011, 19) 156-164
14. Ho, D. D.; Toyoshima, T.; Mo, H.; Kempf, D. J.; Norbeck, D.; Chen, C. M.; Wideburg, N. E.; Burt, S. K.; Erickson, J. W.; Singh, M. K. Characterization of human immunodeficiency virus type 1 variants with increased resistance to a C 2-symmetric protease inhibitor J. Virol. 1994, 68, 2016-2020
15. Weber, I. T. Comparison of the crystal structures and intersubunit interactions of human immunodeficiency and Rous sarcoma virus proteases J. Biol. Chem. 1990, 265, 10492-10496
16. Ishima, R.; Gong, Q.; Tie, Y.; Weber, I. T.; Louis, J. M. Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease Proteins: Struct., Funct., Bioinf. 2010, 78, 1015-1025
17. Mahalingam, B.; Louis, J. M.; Reed, C. C.; Adomat, J. M.; Krouse, J.; Wang, Y. F.; Harrison, R. W.; Weber, I. T. Structural and kinetic analysis of drug resistant mutants of HIV-1 protease Eur. J. Biochem. 1999, 263, 238-245
18. Jarvis, B.; Faulds, D. Nelfinavir. A review of its therapeutic efficacy in HIV infection Drugs 1998, 56, 147-167
19. Liu, F.; Kovalevsky, A. Y.; Louis, J. M.; Boross, P. I.; Wang, Y. F.; Harrison, R. W.; Weber, I. T. Mechanism of drug resistance revealed by the crystal structure of the unliganded HIV-1 protease with F53L mutation J. Mol. Biol. 2006, 358, 1191-1199
20. Pazhanisamy, S.; Stuver, C. M.; Cullinan, A. B.; Margolin, N.; Rao, B. G.; Livingston, D. J. Kinetic characterization of human immunodeficiency virus type-1 protease-resistant variants J. Biol. Chem. 1996, 271, 17979-17985
21. Liu, F.; Boross, P. I.; Wang, Y. F.; Tozser, J.; Louis, J. M.; Harrison, R. W.; Weber, I. T. Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S J. Mol. Biol. 2005, 354, 789-800
22. Liu, F.; Kovalevsky, A. Y.; Tie, Y.; Ghosh, A. K.; Harrison, R. W.; Weber, I. T. Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir J. Mol. Biol. 2008, 381, 102-115
23. Kovalevsky, A. Y.; Tie, Y.; Liu, F.; Boross, P. I.; Wang, Y. F.; Leshchenko, S.; Ghosh, A. K.; Harrison, R. W.; Weber, I. T. Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M J. Med. Chem. 2006, 49, 1379-1387
24. Mahalingam, B.; Wang, Y. F.; Boross, P. I.; Tozser, J.; Louis, J. M.; Harrison, R. W.; Weber, I. T. Crystal structures of HIV protease V82A and L90M mutants reveal changes in the indinavir-binding site Eur. J. Biochem. 2004, 271, 1516-1524
25. Tie, Y.; Kovalevsky, A. Y.; Boross, P.; Wang, Y. F.; Ghosh, A. K.; Tozser, J.; Harrison, R. W.; Weber, I. T. Atomic resolution crystal structures of HIV-1 protease and mutants V82A and I84V with saquinavir Proteins: Struct., Funct., Bioinf. 2007, 67, 232-242
26. Tie, Y.; Boross, P. I.; Wang, Y. F.; Gaddis, L.; Hussain, A. K.; Leshchenko, S.; Ghosh, A. K.; Louis, J. M.; Harrison, R. W.; Weber, I. T. High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains J. Mol. Biol. 2004, 338, 341-352
27. Kovalevsky, A. Y.; Liu, F.; Leshchenko, S.; Ghosh, A. K.; Louis, J. M.; Harrison, R. W.; Weber, I. T. Ultra-high resolution crystal structure of HIV-1 protease mutant reveals two binding sites for clinical inhibitor TMC114 J. Mol. Biol. 2006, 363, 161-173
28. Agniswamy, J.; Shen, C. H.; Aniana, A.; Sayer, J. M.; Louis, J. M.; Weber, I. T. HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements Biochemistry 2012, 51, 2819-2828
29. Kozisek, M.; Bray, J.; Rezacova, P.; Saskova, K.; Brynda, J.; Pokorna, J.; Mammano, F.; Rulisek, L.; Konvalinka, J. Molecular analysis of the HIV-1 resistance development: enzymatic activities, crystal structures, and thermodynamics of nelfinavir-resistant HIV protease mutants J. Mol. Biol. 2007, 374, 1005-1016
30. Ishima, R.; Ghirlando, R.; Tozser, J.; Gronenborn, A. M.; Torchia, D. A.; Louis, J. M. Folded monomer of HIV-1 protease J. Biol. Chem. 2001, 276, 49110-4916
31. Mitsuya, Y.; Winters, M. A.; Fessel, W. J.; Rhee, S. Y.; Hurley, L.; Horberg, M.; Schiffer, C. A.; Zolopa, A. R.; Shafer, R. W. N88D facilitates the co-occurrence of D30N and L90M and the development of multidrug resistance in HIV type 1 protease following nelfinavir treatment failure AIDS Res. Hum. Retroviruses 2006, 22, 1300-1305
32. Mahalingam, B.; Boross, P.; Wang, Y. F.; Louis, J. M.; Fischer, C. C.; Tozser, J.; Harrison, R. W.; Weber, I. T. Combining mutations in HIV-1 protease to understand mechanisms of resistance Proteins: Struct., Funct., Bioinf. 2002, 48, 107-116
33. Henderson, G. J.; Lee, S. K.; Irlbeck, D. M.; Harris, J.; Kline, M.; Pollom, E.; Parkin, N.; Swanstrom, R. Interplay between single resistance-associated mutations in the HIV-1 protease and viral infectivity, protease activity, and inhibitor sensitivity Antimicrob. Agents Chemother. 2012, 56, 623-633
34. Wondrak, E. M.; Louis, J. M. Influence of flanking sequences on the dimer stability of human immunodeficiency virus type 1 protease Biochemistry 1996, 35, 12957-12962
35. Mahalingam, B.; Louis, J. M.; Hung, J.; Harrison, R. W.; Weber, I. T. Structural implications of drug-resistant mutants of HIV-1 protease: high-resolution crystal structures of the mutant protease/substrate analogue complexes Proteins: Struct., Funct., Bioinf. 2001, 43, 455-464
36. Otwinowski, Z.; Minor, W. Processing of X-ray diffraction data collected in oscillation mode. In Methods in Enzymology, Volume 276: Macromolecular Crystallography, Part A; Academic Press: New York, 1997; Vol. 276, pp 307-326.
37. McCoy, A. J.; Grosse-Kunstleve, R. W.; Storoni, L. C.; Read, R. J. Likelihood-enhanced fast translation functions Acta Crystallogr., Sect. D: Biol. Crystallogr. 2005, 61, 458-464
38. Potterton, E.; Briggs, P.; Turkenburg, M.; Dodson, E. A graphical user interface to the CCP4 program suite Acta Crystallogr., Sect. D: Biol. Crystallogr. 2003, 59, 1131-1137
39. Sheldrick, G. M. A short history of SHELX Acta Crystallogr., Sect. A: Found. Crystallogr. 2008, 64, 112-122
40. Emsley, P.; Cowtan, K. Coot: model-building tools for molecular graphics Acta Crystallogr., Sect. D: Biol. Crystallogr. 2004, 60, 2126-2132
41. Chang, Y. C.; Yu, X.; Zhang, Y.; Tie, Y.; Wang, Y. F.; Yashchuk, S.; Ghosh, A. K.; Harrison, R. W.; Weber, I. T. Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1′-pyrrolidinone ring J. Med. Chem. 2012, 55, 3387-3397