jm8b00336_si_005.pdb (188.03 kB)

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

Download (188.03 kB)
posted on 02.04.2018, 00:00 by Haruka Sekiguchi, Tomoko Kuroyanagi, David Rhainds, Kazuya Kobayashi, Yuka Kobayashi, Hiroaki Ohno, Nikolaus Heveker, Kenichi Akaji, Nobutaka Fujii, Shinya Oishi
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.