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.
Fujii
N
N
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. nfujii@pharm.kyoto-u.ac.jp
Tamamura
H
H
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019743:Chemokines, CXC / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D019743:Chemokines, CXC; D019718:Receptors, CXCR4