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 transcriplase 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 angstrom resolution by X-ray crystallography. The conformations adopted by the enzyme-bound TCs were analyzed and compared with those of bioisosterically related NNRTIs.
|Titolo:||Crystal structures of HIV-1 reverse transcriptase complexes with thiocarbamate non-nucleoside inhibitors|
|Autori interni:||BOLOGNESI, MARTINO (Ultimo)|
|Parole Chiave:||HIV-1 ; reverse transcriptase ; X-ray crystallography ; non-nucleoside reverse transcriptase inhibitors ; thiocarbamates|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||2008|
|Digital Object Identifier (DOI):||10.1016/j.bbrc.2007.11.036|
|Appare nelle tipologie:||01 - Articolo su periodico|