Peptide-lead CXCR4 antagonists with high anti-HIV activity.

Abstract

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.

• Authors: N Fujii, H Tamamura
• Journal: Current opinion in investigational drugs (London, England : 2000) (Curr Opin Investig Drugs) Vol. 2 Issue 9 Pg. 1198-202 (Sep 2001) ISSN: 1472-4472 [Print] England
• PMID: 11717804 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Anti-HIV Agents
• Chemokines, CXC
• Receptors, CXCR4

Topics

• Amino Acid Sequence
• Anti-HIV Agents (chemical synthesis, chemistry, pharmacology)
• Chemokines, CXC (metabolism)
• Humans
• Molecular Sequence Data
• Receptors, CXCR4 (antagonists & inhibitors)
• Structure-Activity Relationship