A Synthetic Peptide Fragment Derived from RANTES is a Potent Inhibitor of HIV-1 Infectivity Despite a Surprising Lack of CCR5 Receptor Affinity

CCR5 (CC-chemokine receptor 5) is a key co-receptor, in concert with CD4, for infectivity of HIV-1 (human immunodeficiency virus type-1) into healthy human cells, and RANTES, an endogenous ligandfor CCR5, is a potent inhibitor of HIV-1 infectivity. In this structure-activity relationship (SAR) study, peptide fragments derived from RANTES were designed, synthesized and evaluated fortheir ability to inhibit HIV-1 infectivity. The goal was to determine the effect of peptide length on anti-HIV activity and to obtain an optimally sized RANTES peptide probe for further SAR studies. The analogue Ac[Ala^10,11]RANTES-(1–14)NH₂, AA14, was identified as an effective inhibitor of HIV-1 infectivity at 10 nM but despite the functional activity, surprisingly it did not exhibit any notable affinity for the CCR5 chemokine receptor. Further, increasing peptide size enhanced neither the inhibition of HIV-1 infectivity nor CCR5 receptor affinity. As a potent inhibitor of HIV-1 infectivity,the lead analogue most likely utilizes a different (and currentlyunknown) mechanism than interaction with CCR5 for anti-HIV activity.     

Analogues of N-terminal truncated synthetic peptide fragments derived from RANTES inhibit HIV-1 infectivity

A series of synthetic peptide fragments derived from RANTES were designed, synthesized, and evaluated to determine the effect of N-terminal truncation on the ability of the lead compound Ac[Ala(10,11)]RANTES-(1-14)NH(2) to inhibit HIV-1 infectivity. Both the lead compound and the truncated analogue Ac[Ala(10,11)]RANTES-(3-14)NH(2) were able to significantly inhibit HIV-1 infectivity. These results suggest that a small synthetic peptide may be able to mimic RANTES and have the ability to prevent transmission of HIV-1.     

A Synthetic Peptide Fragment Derived from RANTES is a Potent Inhibitor of HIV-1 Infectivity Despite a Surprising Lack of CCR5 Receptor Affinity

Summary CCR5 (CC-chemokine receptor 5) is a key co-receptor, in concert with CD4, for infectivity of HIV-1 (human immunodeficiency virus type-1) into healthy human cells, and RANTES, an endogenous ligand for CCR5, is a potent inhibitor of HIV-1 infectivity. In this structure-activity relationship (SAR) study, peptide fragments derived from RANTES were designed, synthesized and evaluated for their ability to inhibit HIV-1 infectivity. The goal was to determine the effect of peptide length on anti-HIV activity and to obtain an optimally sized RANTES peptide probe for further SAR studies. The analogue Ac[Ala^10,11]RANTES-(1–14)NH₂, AA14, was identified as an effective inhibitor of HIV-1 infectivity at 10 nM but despite the functional activity, surprisingly it did not exhibit any notable affinity for the CCR5 chemokine receptor. Further, increasing peptide size enhanced neither the inhibition of HIV-1 infectivity nor CCR5 receptor affinity. As a potent inhibitor of HIV-1 infectivity, the lead analogue most likely utilizes a different (and currently unknown) mechanism than interaction with CCR5 for anti-HIV activity.