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

Citation:

Hayouka, Z. ; Hurevich, M. ; Levin, A. ; Benyamini, H. ; Iosub, A. ; Maes, M. ; Shalev, D. E. ; Loyter, A. ; Gilon, C. ; Friedler, A. . Cyclic Peptide Inhibitors Of Hiv-1 Integrase Derived From The Ledgf/P75 Protein. BIOORGANIC & MEDICINAL CHEMISTRY 2010, 18, 8388-8395.

Date Published:

DEC 1

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. (C) 2010 Elsevier Ltd. All rights reserved.

Publisher's Version

Last updated on 09/04/2023