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Peptides that inhibit HIV‐1 integrase by blocking its protein–protein interactions
Author(s) -
Maes Michal,
Loyter Abraham,
Friedler Assaf
Publication year - 2012
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2012.08680.x
Subject(s) - integrase , small molecule , protein–protein interaction , integrase inhibitor , drug development , drug discovery , biology , computational biology , viral protein , human immunodeficiency virus (hiv) , chemistry , drug , biochemistry , microbiology and biotechnology , dna , virus , virology , antiretroviral therapy , pharmacology , viral load
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.