Inhibition of human immunodeficiency virus type-1 reverse transcriptase by a novel peptide derived from the viral integrase.
Previous studies show that the reverse transcriptase (RT) of human immunodeficiency virus type-1 (HIV-1) and RT-derived peptides interact with and inhibit the viral integrase (IN). In the present study, we have performed the complementary study by screening a complete library of HIV-1 IN-derived peptides for their effects on the RT. We have identified a 20-residues long peptide, derived from the IN (residues 46-65) that binds the RT and inhibits its DNA-polymerase activities (without affecting the ribonuclease-H activity). The full 20-residues sequence is required for maximal inhibition. This inhibition is non-competitive and probably results from obstructing the formation of RT-DNA complexes by the peptide. The data and the molecular docking model presented suggest that this inhibition is probably caused by a steric hindrance or conformational changes of the RT. These results can facilitate the development of novel and specific peptide-based HIV-1 RT inhibitors that might help in the fight against AIDS.
Oz Gleenberg
Iris
I
Department of Cell and Developmental Biology, The Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Herschhorn
Alon
A
Goldgur
Yehuda
Y
Hizi
Amnon
A
D000595:Amino Acid Sequence; D004247:DNA / Q000378:metabolism; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology*; D019151:Peptide Library; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D010446:Peptide Fragments; D019151:Peptide Library; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D004247:DNA; D019427:HIV Integrase; D054303:HIV Reverse Transcriptase