Integrase model

The HlV-1 protease is responsible for processing the protein precursors to the enzymes (integrase, protease and reverse transcriptase) and the structural proteins of the HIV-1 virus. Maw and Hall found that topological indices provide rehable QSAR models for the IC50 data of 32 HIV-1 protease inhibitors [29]. The best QSAR model, with r = 0.86, s=0.60 and q = 0.79, was obtained with the shape index Ka, the connechvity index the sum of HE-state indices for ah groups that act as... 

Improving free fraction continues to be a goal in the anti-infective area, particularly in areas where animal efficacy models are not readily available. The importance of adequate free fraction was noted in publications describing a series of HIV integrase inhibitors [52], the HCV protease inhibitor VX-950 [53], a series of cyclosporine derivatives active against HCV [54], and a series of antibacterial MurB inhibitors [55]. 

Liao, C.Z., Karki, R.G., Marchand, C., Pommier, Y., Nicklaus, M.C. Virtual screening application of a model of full-length HIV-1 integrase complexed with viral DNA. Bioorg. Med. Chem. Lett. 2007, 17, 5361-5. 

Developing a dynamic pharmacophore model for HIV-1 integrase. J. Med. Chem. 43 2100-14... 

Iyer, M. and Hopfinger, A.J. (2007) Treating chemical diversity in QSAR analysis modeling diverse HIV-1 integrase inhibitors using 4D fingerprints. 

Carlson HA, Masukawa KM, Rubins K, Bushman FD, Jorgenses WL, Lins RD, Briggs JM, McCammon JA. Developing a dynamic pharmacophore model for HIV-1 integrase. J Med Chem 2000 43 2100-2114. 

Jorgensen, W.L, Lins, R.D., Briggs, J.M., and McCammon, J.A. (2000) Developing a dynamic pharmacophore model for FllV-1 integrase. Journal of Medicinal Chemistry, 43 (11), 2100-2114. 

Wang et al. reported the application of an X-ray structure-derived pharmacophore model to identify novel HIV-1 protease inhibitors. After searching the NCI database (206 000 molecules), testing of 50 molecules resulted in submicromolar activity for the best 2 compounds [149]. In a search for HIV-1 integrase inhibitors, a protein-derived pharmacophore mode] produced 340 hits from 10 different classes. Four compounds vere sho vn to have affinities <30 pM [150] against this enzyme. 

Deng J, Lee KW, Sanchez T, Cui M, Neamati N, Briggs JM (2005) Dynamic receptor-based pharmacophore model development and its application in designing novel HIV-1 integrase inhibitors. J Med Chem 48(5) 1496-1505... 

Voziyanov 1, Pathania S, Jayaram M. A general model for site-specific recombination by the integrase family recombinases. Nucleic Acid Res 1999 27 930-941. 

Bernardi, R, Bottoni, A., De Vivo, M., Garavelli, M., Keseru, G. M., 8c Ndray-Szab6, G. (2002). A hypothetical mechanism for HIV-1 integrase catalytic action DFT modelling of a bio-mimetic environment. Chemical Physics Letters, 362,1. 

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