AIDSWEEKLY Plus; Monday, August 15, 2005
Staff Medical Writers

According to recent research from Israel, "Recent studies have shown that the integrase (IN) of HIV-1 is inhibited in vitro by HIV-1 reverse transcriptase (RT).

"We further investigated the specific protein sequences of RT that were involved in this inhibition by screening a complete library of RT-derived peptides for their inhibition of IN activities."

"Two 20-residue peptides, peptide 4286, derived from the RT DNA polymerase domain, and the one designated 4321, from the RT ribonuclease H domain, inhibit the enzymatic activities of IN in vitro.

"The former peptide inhibits all three IN-associated activities (3'-end processing, strand transfer, and disintegration), whereas the latter one inhibits primarily the first two functions. We showed the importance of the sequences and peptide length for the effective inhibition of IN activities," reported I.O. Gleenberg and coworkers at Tel Aviv University.

"Binding assays of the peptides to IN (with no DNA substrate present) indicated that the two inhibitory peptides (as well as several noninhibitory peptides) interact directly with IN. Moreover," said researchers, "the isolated catalytic core domain of IN also interacted directly with the two inhibitory peptides."

"Nevertheless," Gleenberg continued, "only peptide 4286 can inhibit the disintegration activity associated with the IN core domain, because this activity is the only one exhibited by this domain. This result was expected from the lack of inhibition of disintegration of full-length IN by peptide 4321."

"The data and the 3-dimensional models presented suggested that the inhibition resulted from steric hindrance of the catalytic domain of IN. This information can substantially facilitate the development of novel drugs against HIV INs and thus contribute to the fight against AIDS," the authors concluded.

Gleenberg and colleagues published their study in the Journal of Biological Chemistry (Peptides derived from the reverse transcriptase of human immunodeficiency virus type 1 as novel inhibitors of the viral integrase. J Biol Chem. 2005 Jun 10;280(23):21987-96.

For additional information, contact A. Hizi, Tel Aviv University, Sackler School of Medicine, Dept. Cell & Development Biology, IL-69978 Tel Aviv, Israel.

Publisher contact information for the Journal of Biological Chemistry is: American Society Biochemistry Molecular Biology Inc., 9650 Rockville Pike, Bethesda, MD 20814-3996, USA.

Keywords: Tel Aviv, Israel, HIV/AIDS, Viral Integrase Inhibitor, Reverse Transcriptase, Peptides, Pharmaceutical & Drug Development.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Oz Gleenberg I, Avidan O, Goldgur Y, et al., Peptides derived from the reverse transcriptase of human immunodeficiency virus type 1 as novel inhibitors of the viral integrase., J Biol Chem. 2005 Jun 10;280(23):21987-96.

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