Enhancement of anti-HIV-1 activity by hot spot evolution of RANTES-derived peptides

Massimiliano Secchi, Renato Longhi, Lia Vassena, Francesca Sironi, Stephan Grzesiek, Paolo Lusso, Luca Vangelista

Research output: Contribution to journalArticlepeer-review


CCR5, the major HIV-1 coreceptor, is a primary target for HIV-1 entry inhibition strategies. CCL5/RANTES, a natural CCR5 ligand, is one of the most potent HIV-1 entry inhibitors and, therefore, an ideal candidate to derive HIV-1 blockers. Peptides spanning the RANTES N-loop/β1-strand region act as specific CCR5 antagonists, with their hydrophobic N- and C termini playing a crucial role in virus blockade. Here, hydrophobic surfaces were enhanced by tryptophan substitution of aromatic residues, highlighting position 27 as a critical hot spot for HIV-1 blockade. In a further molecular evolution step, C-terminal engraftment of RANTES 40′ loop produced a peptide with the highest solubility and anti-HIV-1 activity. These modified peptides represent leads for the development of effective HIV-1 inhibitors and microbicides.

Original languageEnglish
Pages (from-to)1579-1588
Number of pages10
JournalChemistry and Biology
Issue number12
Publication statusPublished - Dec 21 2012

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Molecular Biology
  • Clinical Biochemistry
  • Molecular Medicine
  • Pharmacology


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