Crystal structures of HIV-1 reverse transcriptase complexes with thiocarbamate non-nucleoside inhibitors

Andrea Spallarossa, Sara Cesarini, Angelo Ranise, Marco Ponassi, Torsten Unge, Martino Bolognesi

Research output: Contribution to journalArticlepeer-review

Abstract

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 Å resolution by X-ray crystallography. The conformations adopted by the enzyme-bound TCs were analyzed and compared with those of bioisosterically related NNRTIs.

Original languageEnglish
Pages (from-to)764-770
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume365
Issue number4
DOIs
Publication statusPublished - Jan 25 2008

Keywords

  • HIV-1
  • Non-nucleoside reverse transcriptase inhibitors
  • Reverse transcriptase
  • Thiocarbamates
  • X-ray crystallography

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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