Nuclear magnetic resonance studies of CXC chemokine receptor 4 allosteric peptide agonists in solution

Publisher Website
Google Scholar
Abstract
Abstract:  CXC chemokine receptor 4 (CXCR4) is an important pharmacological target due to its involvement in HIV‐1 pathogenesis and cancer metastasis. Two recently discovered allosteric agonists that bind and activate CXCR4, the ASLW and RSVM peptides, were analyzed using solution nuclear magnetic resonance spectroscopy. Both peptides assumed an extended backbone conformation with several well‐defined local motifs in the regions from residues 5 to 8 and 9 to 12. The local structures in the region of residues 5–8 were different for agonists studied here and natural ligands. The local structure in the region 9–12 was adopted by the entire ensemble of the ASLW peptide structures and by the subset of conformations for the RSVM peptide. The same turn was found in full‐length stromal derived factor (SDF)‐1 and in the small family of the SDF‐1 N‐terminal 17‐mer. Similar examples in literature suggest the relevance of nascent structures in peptides to their biologically relevant conformations. The significance of found local structures and implications for further drug design are discussed.