title: Peptides that inhibit HIV-1 integrase by blocking its protein-protein interactions.
abstract: HIV-1 integrase (IN) is one of the key enzymes in the viral replication cycle. It mediates the integration of viral cDNA into the host cell genome. IN activity requires interactions with several viral and cellular proteins, as well as IN oligomerization. Inhibition of IN is an important target for the development of anti-HIV therapies, but there is currently only one anti-HIV drug used in the clinic that targets IN. Several other small-molecule anti-IN drug leads are either undergoing clinical trials or in earlier stages of development. These molecules specifically inhibit one of the IN-mediated reactions necessary for successful integration. However, small-molecule inhibitors of protein-protein interactions are difficult to develop. In this review, we focus on peptides that inhibit IN. Peptides have advantages over small-molecule inhibitors of protein-protein interactions: they can mimic the structures of the binding domains within proteins, and are large enough to competitively inhibit protein-protein interactions. The development of peptides that bind IN and inhibit its protein-protein interactions will increase our understanding of the IN mode of action, and lead to the development of new drug leads, such as small molecules derived from these peptides, for better anti-HIV therapy.
authors: Institute of Chemistry, The Hebrew University of Jerusalem, Israel.
authors: Michal
authors: M
authors: Maes
authors: Abraham
authors: A
authors: Loyter
authors: Assaf
authors: A
authors: Friedler
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D004353:Drug Evaluation, Preclinical; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D010446:Peptide Fragments / Q000494:pharmacology; D019151:Peptide Library; D010455:Peptides / Q000494:pharmacology*; D055503:Protein Multimerization / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; C548807:LEDGF peptide (361-370), human; D010446:Peptide Fragments; D019151:Peptide Library; D010455:Peptides; D019427:HIV Integrase; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; C514801:p31 integrase protein, Human immunodeficiency virus 1