Crystal structures of HIV-1 reverse transcriptase complexes with thiocarbamate non-nucleoside inhibitors
- Dipartimento di Scienze Farmaceutiche, Universita di Genova, viale Benedetto XV, 3, I-16132 Genova (Italy)
- Istituto Nazionale per la Ricerca sul Cancro (IST), Largo Rosanna Benzi, 10, I-16132 Genova (Italy)
- Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Box 596, SE-751 24 Uppsala (Sweden)
- Department of Biomolecular Sciences and Biotechnology, CNR-INFM, University of Milano, Via Celoria 26, I-20131 Milan (Italy)
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 2.8-3.0 A resolution by X-ray crystallography. The conformations adopted by the enzyme-bound TCs were analyzed and compared with those of bioisosterically related NNRTIs.
- OSTI ID:
- 21043590
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 365; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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