A Conformationalry Frozen Peptoid Boosts GXCR4 Affinity and Anti-HIV Activity

摘要

The chemokine receptor subtype CXCR4 belongs to the G-protein coupled receptors (GPCRs) and is, together with its natural ligand CXCL12 (or SDF-1), a central part of the signaling system in the human body. Its functions range from stem-cell trafficking during embryogenesis, through cardiovascular, hematopoietic, and brain development, to signaling in the nervous and immune system. Furthermore, CXCR4 is one of two major coreceptors used by the human immunodeficiency virus (HIV) for cell entry and CXCR4-using viruses are critical for the pathogenesis of AIDS. Hence, CXCR4 represents a valuable therapeutic option for multiple diseases, such as inflammation, cancer, and HIV/ AIDS. The recent approval of the CXCR4 antagonist AMD3100 (Mozobil) as a drug for stem-cell mobilization paves the way for development of further compounds that target CXCR4 related diseases.'111' However at present, none of the FDA-approved anti-HIV drugs target the CXCR4 receptor.