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 journalArticle

9 Citations (Scopus)

Abstract

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
Volume19
Issue number12
DOIs
Publication statusPublished - Dec 21 2012
Externally publishedYes

Fingerprint

Chemokine CCL5
HIV-1
Peptides
Anti-Infective Agents
Viruses
Tryptophan
Substitution reactions
Solubility
HIV Fusion Inhibitors
Ligands
Molecular Evolution

ASJC Scopus subject areas

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

Cite this

Enhancement of anti-HIV-1 activity by hot spot evolution of RANTES-derived peptides. / Secchi, Massimiliano; Longhi, Renato; Vassena, Lia; Sironi, Francesca; Grzesiek, Stephan; Lusso, Paolo; Vangelista, Luca.

In: Chemistry and Biology, Vol. 19, No. 12, 21.12.2012, p. 1579-1588.

Research output: Contribution to journalArticle

Secchi, M, Longhi, R, Vassena, L, Sironi, F, Grzesiek, S, Lusso, P & Vangelista, L 2012, 'Enhancement of anti-HIV-1 activity by hot spot evolution of RANTES-derived peptides', Chemistry and Biology, vol. 19, no. 12, pp. 1579-1588. https://doi.org/10.1016/j.chembiol.2012.10.007
Secchi M, Longhi R, Vassena L, Sironi F, Grzesiek S, Lusso P et al. Enhancement of anti-HIV-1 activity by hot spot evolution of RANTES-derived peptides. Chemistry and Biology. 2012 Dec 21;19(12):1579-1588. https://doi.org/10.1016/j.chembiol.2012.10.007
Secchi, Massimiliano ; Longhi, Renato ; Vassena, Lia ; Sironi, Francesca ; Grzesiek, Stephan ; Lusso, Paolo ; Vangelista, Luca. / Enhancement of anti-HIV-1 activity by hot spot evolution of RANTES-derived peptides. In: Chemistry and Biology. 2012 ; Vol. 19, No. 12. pp. 1579-1588.
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