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NLM AIDSLINE
A new potent HIV-1 reverse transcriptase inhibitor. A synthetic peptide derived from the interface subunit domains.
Morris MC; Robert-Hebmann V; Chaloin L; Mery J; Heitz F; Devaux C; Goody
December 30, 1999
J Biol Chem. 1999 Aug 27;274(35):24941-6. Unique Identifier : AIDSLINE

The biologically relevant and active forms of human immunodeficiency viruses type 1 and 2 reverse transcriptase found in infectious virions are heterodimers produced in a two-step dimerization process. Dimerization involves first the rapid association of the two subunits, followed by a slow conformational change yielding a fully active form. We have shown that the dimeric nature of reverse transcriptase represents a important target for the design of a new class of antiviral agents. In this work, we propose a new strategy for its inhibition by targeting protein/protein interactions during viral formation in infected cells. From the screening of peptides derived from the tryptophan cluster at the interface of the connection subdomain, we have designed a short peptide (10 residues) corresponding to residues 395-404, which can block dimerization of reverse transcriptase in vitro and in infected cells. This peptide is highly efficient in abolishing the production of viral particles, without any adverse toxic side effects, when transduced into human immunodeficiency virus type 1-infected cells together with a new peptide carrier.

JOURNAL ARTICLE Amino Acid Sequence Antiviral Agents/CHEMISTRY/PHARMACOLOGY Cell Line Dimerization Drug Design Enzyme Stability/DRUG EFFECTS Human HIV-1 Reverse Transcriptase/*ANTAGONISTS & INHIB/CHEMISTRY/ *CHEMICAL SYNTHESIS/PHARMACOLOGY Kinetics Microscopy, Fluorescence Models, Molecular Molecular Sequence Data Peptide Fragments/*CHEMICAL SYNTHESIS/PHARMACOLOGY Protein Conformation Reverse Transcriptase Inhibitors/*CHEMICAL SYNTHESIS/PHARMACOLOGY Support, Non-U.S. Gov't

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