ABSTRACT
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.
Subject(s)
Peptides, Cyclic/chemistry , Peptides, Cyclic/pharmacology , Receptors, CXCR/metabolism , Amino Acid Substitution , HEK293 Cells , Humans , Ligands , Models, Molecular , Molecular Structure , Receptors, CXCR/chemistry , Structure-Activity RelationshipABSTRACT
A series of novel 3,4,7-trisubstituted benzofuran derivatives were synthesized, and their binding affinity to κ- (KOR) and µ-opioid receptors (MOR) were evaluated. Several aryl ethers showed moderate binding activities to KOR (IC50=3.9-11 µM) without binding to MOR.
