Models which explain the inhibition of reverse transcriptase by HIV-1-specific (thio)carboxanilide derivatives.

摘要: The (thio)carboxanilide derivatives are potent and selective inhibitors of HIV-1 reverse transcriptase (RT) have a favourable antiviral activity spectrum. To understand better their mode action, to provide structural basis for further improvement, models RT complexed with four (UC781, UC10, UC38 UC84) been constructed based on the X-ray structure 9-chloro-TIBO. In models, protein conformation is similar that RT-TIBO complex complexes stabilised by hydrogen bonding between main chain oxygen Lys101. Significant hydrophobic interactions include those Leu100, Val106, Val179, Tyr188, Phe227, Leu234, His235. thiocarboxanilides UC781 UC10 also make important Trp229. consistent inhibitors' relative potencies observed resistance data. They predict mutations Trp229, or Leu234 might confer resistance. Since these not observed, some constraining functional role residues in active enzyme suggested.