Peptide-lead CXCR4 antagonists with high anti-HIV activity

The highly selective CXCR4 antagonist, T-22 ([Tyr5,12,Lys7]-polyphemusin II), and its shortened potent analogs, T-140 and TC-14012, strongly inhibit T-cell line-tropic HIV-1 (X4-HIV-1) infection through their specific binding to a chemokine receptor, CXCR4. These peptides were found through studies of the structure-activity relationships of tachyplesins and polyphemusins, which function as self-defence peptides of horseshoe crab's immature immune systems. T-140 and TC-14012 possess the highest level of anti-HIV activity and antagonism of target cell entry by X4-HIV-1 among all the CXCR4 antagonists that have been reported to date.