TY - JOUR
T1 - Enhancement of anti-HIV-1 activity by hot spot evolution of RANTES-derived peptides
AU - Secchi, Massimiliano
AU - Longhi, Renato
AU - Vassena, Lia
AU - Sironi, Francesca
AU - Grzesiek, Stephan
AU - Lusso, Paolo
AU - Vangelista, Luca
N1 - Funding Information:
We thank Sébastien Morin for stimulating discussion and critical reading of the manuscript, Gabriella Scarlatti for providing pediatric HIV-1 isolates, and the NIH AIDS Research and Reference Reagent Program for providing primary HIV-1 isolates. This work was supported in part by the European Microbicides Project (FP6 Grant LSHP-CT-2003-503558) and the Combined Highly Active Anti-Retroviral Microbicides Project (FP7/2007-2013 Grant 242135), Brussels, Belgium, European Union.
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/12/21
Y1 - 2012/12/21
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chembiol.2012.10.007
DO - 10.1016/j.chembiol.2012.10.007
M3 - Article
C2 - 23261601
AN - SCOPUS:84871569866
VL - 19
SP - 1579
EP - 1588
JO - Cell Chemical Biology
JF - Cell Chemical Biology
SN - 2451-9448
IS - 12
ER -