Cyclic peptide inhibitors of HIV-1 integrase derived from the LEDGF/p75 protein

Citation:

Hayouka Z., M., Hurevich , A., Levin , H., Benyamini , A., Iosub , M., Maes , E., Shalev D. , A., Loyter , C., Gilon , and A., Friedler . 2010. “Cyclic Peptide Inhibitors Of Hiv-1 Integrase Derived From The Ledgf/P75 Protein”. Bioorg. Med. Chem. https://www.sciencedirect.com/science/article/pii/S0968089610008837?via%3Dihub.

Abstract:

Restricting linear peptides to their bioactive conformation is an attractive way of improving their stability and activity. We used a cyclic peptide library with conformational diversity for selecting an active and stable peptide that mimics the structure and activity of the HIV-1 integrase (IN) binding loop from its cellular cofactor LEDGF/p75 (residues 361–370). All peptides in the library had the same primary sequence, and differed only in their conformation. Library screening revealed that the ring size and linker structure had a huge effect on the conformation, binding and activity of the peptides. One of the cyclic peptides, c(MZ 4-1), was a potent and stable inhibitor of IN activity in vitro and in cells even after 8 days. The NMR structure of c(MZ 4-1) showed that it obtains a bioactive conformation that is similar to the parent site in LEDGF/p75.