Structure–Activity Relationship Study of Cyclic Pentapeptide Ligands for Atypical Chemokine Receptor 3 (ACKR3)

The
atypical chemokine receptor 3 (ACKR3)/CXC chemokine receptor
7 (CXCR7) recognizes stromal cell-derived factor 1 (SDF-1)/CXCL12
and is involved in a number of physiological and pathological processes.
Here, we investigated the SAR of the component amino acids in an ACKR3-selective
ligand, FC313 [cyclo(-d-Tyr-l-Arg-l-MeArg-l-Nal­(2)-l-Pro-)], for the development
of highly active ACKR3 ligands. Notably, modification at the l-Pro position with a bulky hydrophobic side chain led to improved
bioactivity toward ACKR3.

非典型趋化因子受体3（atypical chemokine receptor 3, ACKR3）/CXC趋化因子受体7（CXC chemokine receptor 7, CXCR7）可识别基质细胞衍生因子1（stromal cell-derived factor 1, SDF-1）/CXCL12，并参与诸多生理与病理过程。本研究针对ACKR3选择性配体FC313[环(-d-Tyr-l-Arg-l-MeArg-l-Nal(2)-l-Pro-)]的组成氨基酸开展了构效关系（structure-activity relationship, SAR）研究，以开发高活性的ACKR3配体。值得注意的是，在l-脯氨酸（l-Pro）位点引入大体积疏水侧链，可提升其对ACKR3的生物活性。