Scientific article

Highly potent HIV inhibition: engineering a key anti-HIV structure from PSC-RANTES into MIP-1 beta/CCL4

Published inProtein engineering, design & selection, vol. 21, no. 2, p. 65-72
Publication date2008

The HIV coreceptor CCR5 is a validated target for both the prevention and therapy of HIV infection. PSC-RANTES, an N-terminally modified analogue of one of the natural chemokine ligands of CCR5 (RANTES/CCL5), is a potent inhibitor of HIV entry into target cells. Here, we set out to engineer the anti-HIV activity of PSC-RANTES into another natural CCR5 ligand (MIP-1beta/CCL4), by grafting into it the key N-terminal pharmacophore region from PSC-RANTES. We were able to identify MIP-1beta/CCL4 analogues that retain the receptor binding profile of MIP-1beta/CCL4, but acquire the very high anti-HIV potency and characteristic inhibitory mechanism of PSC-RANTES. Unexpectedly, we discovered that in addition to N-terminal structures from PSC-RANTES, the side chain of Lys33 is also necessary for full anti-HIV potency.

  • Amino Acid Sequence
  • Anti-HIV Agents/chemical synthesis
  • Cells Cultured
  • Chemokine CCL4/genetics/therapeutic use
  • Chemokine CCL5/genetics/therapeutic use
  • Drug Design
  • HIV/drug effects
  • Humans
  • Molecular Sequence Data
  • Structure-Activity Relationship
Citation (ISO format)
GAERTNER, Hubert François et al. Highly potent HIV inhibition: engineering a key anti-HIV structure from PSC-RANTES into MIP-1 beta/CCL4. In: Protein engineering, design & selection, 2008, vol. 21, n° 2, p. 65–72. doi: 10.1093/protein/gzm079
Main files (1)
Article (Accepted version)
ISSN of the journal1741-0126

Technical informations

Creation02/16/2009 4:59:00 PM
First validation02/16/2009 4:59:00 PM
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