Crystal structures of HIV-1 reverse transcriptase complexes with thiocarbamate non-nucleoside inhibitors
2008 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, Vol. 365, no 4, 764-770 p.Article in journal (Refereed) Published
O-Phthalimidoethyl-N-arylthiocarbamates (TCs) have been recently identified as a new class of potent HIV-1 reverse transcriptase (RT) non-nucleoside inhibitors (NNRTIs), by means of computer-aided drug design techniques [Ranise A. Spallarossa, S. Cesarini, F. Bondavalli, S. Schenone, O. Bruno, G. Menozzi, P. Fossa, L. Mosti, M. La Colla, et al., Structure-based design, parallel synthesis, structure-activity relationship, and molecular modeling studies of thiocarbamates, new potent non-nucleoside HIV-1 reverse transcriptase inhibitor isosteres of phenethylthiazolylthiourea derivatives, J. Med. Chem. 48 (2005) 3858-3873]. To elucidate the atomic details of RT/TC interaction and validate an earlier TC docking model, the structures of three RT/TC complexes were determined at 2.8-3.0A resolution by X-ray crystallography. The conformations adopted by the enzyme-bound TCs were analyzed and compared with those of bioisosterically related NNRTIs.
Place, publisher, year, edition, pages
2008. Vol. 365, no 4, 764-770 p.
HIV-1, reverse transcriptase, X-ray crystallography, non-nucleoside reverse transcriptase inhibitors, thiocarbamates
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:uu:diva-14260DOI: 10.1016/j.bbrc.2007.11.036ISI: 000251867100026PubMedID: 18035053OAI: oai:DiVA.org:uu-14260DiVA: diva2:42030