Structure-based HIV-1 integrase inhibitor design: a future perspective
- 24 February 2001
- journal article
- review article
- Published by Informa Healthcare in Expert Opinion on Investigational Drugs
- Vol. 10 (2) , 281-296
- https://doi.org/10.1517/13543784.10.2.281
Abstract
The pol gene of HIV-1 encodes for three essential enzymes, protease (PR), reverse transcriptase (RT) and integrase (IN). More than 16 drugs, targeting two of these enzymes, PR and RT have been approved by the FDA. At present, there are no clinically useful agents that inhibit the third enzyme, IN. Combination chemotherapy consisting of PR and RT inhibitors has shown remarkable success in the clinic and has benefited many patients. It is thought that a combination of drugs targeting all three enzymes should further incapacitate the virus. Discovery of highly selective PR inhibitors owe their success to the recent development in structure-guided drug design. During the past several years a plethora of structures of HIV-1 PR in complex with an inhibitor have been solved by x-ray crystallography. This incredible wealth of information provided opportunities for the discovery of second and third generation inhibitors. Due to the inherent nature of IN and insufficient structural information, structure-based inhi...Keywords
This publication has 66 references indexed in Scilit:
- X-ray structure of simian immunodeficiency virus integrase containing the core and C-terminal domain (residues 50-293) - an initial glance of the viral DNA binding platform 1 1Edited by I. A. WilsonJournal of Molecular Biology, 2000
- Solution structure of the His 12 → Cys mutant of the N-terminal zinc binding domain of HIV-1 integrase complexed to cadmiumProtein Science, 1998
- Crystal structures of the catalytic domain of HIV-1 integrase free and complexed with its metal cofactor: high level of similarity of the active site with other viral integrases 1 1Edited by R. HuberJournal of Molecular Biology, 1998
- A Proposal for the Mg2+ Binding Site of P-Type Ion Motive ATPases and the Mechanism of Phosphoryl Group TransferBiochemistry, 1997
- LESSONS FROM ZINC-BINDING PEPTIDESAnnual Review of Biophysics, 1997
- The catalytic domain of human immunodeficiency virus integrase: ordered active site in the F185H mutantFEBS Letters, 1996
- Triterpenes as Potential Dimerization Inhibitors of HIV-1 ProteaseBiochemical and Biophysical Research Communications, 1996
- The High Resolution Crystal Structure of the DNA Decamer d(AGGCATGCCT)Journal of Molecular Biology, 1996
- High-resolution Structure of the Catalytic Domain of Avian Sarcoma Virus IntegraseJournal of Molecular Biology, 1995
- Mg2+ Binding to the Active Site of EcoRV Endonuclease: A Crystallographic Study of Complexes with Substrate and Product DNA at 2-.ANG. ResolutionBiochemistry, 1995