Crystal structures of novel allosteric peptide inhibitors of HIV integrase identify new interactions at the LEDGF binding site

David I. Rhodes, Thomas S. Peat, Nick Vandegraaff, Dharshini Jeevarajah, Janet Newman, John Martyn, Jonathan A.V. Coates, Nicholas J. Ede, Philip Rea, John J. Deadman

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31 Citations (Scopus)


An optimised method of solution cyclisation gave us access to a series of peptides including SLKIDNLD (2). We investigated the crystallographic complexes of the HIV integrase (HIV-IN) catalytic core domain with 13 of the peptides and identified multiple interactions at the binding site, including hydrogen bonds with residues Thr125 and Gln95, that have not previously been described as being accessible within the binding site. We show that the peptides inhibit the interaction of lens epithelium-derived growth factor (LEDGF) with HIV-IN in a proximity AlphaScreen assay and in an assay for the LEDGF enhancement of HIV-IN strand transfer. The interactions identified represent a potential framework for the development of new HIV-IN inhibitors.

Original languageEnglish
Pages (from-to)2311-2315
Number of pages5
Issue number15
Publication statusPublished - 17 Oct 2011
Externally publishedYes


  • Co-crystal structures
  • Cyclic peptides
  • HIV-1 integrase
  • Inhibitors

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