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 language | English |
|---|---|
| Pages (from-to) | 1579-1588 |
| Number of pages | 10 |
| Journal | Chemistry and Biology |
| Volume | 19 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 21 2012 |
| Externally published | Yes |
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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 journal › Article
}
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
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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UR - http://www.scopus.com/inward/citedby.url?scp=84871569866&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2012.10.007
DO - 10.1016/j.chembiol.2012.10.007
M3 - Article
VL - 19
SP - 1579
EP - 1588
JO - Cell Chemical Biology
JF - Cell Chemical Biology
SN - 2451-9448
IS - 12
ER -