Selective Pyrophosphate Recognition by Cyclic Peptide Receptors in Physiological Saline

The anion binding ability of a family of bis(Zn^II‐Dpa) functionalized cyclic peptides has been investigated using displacement assays with a fluorescent coumarin indicator in water, saline solution, and Krebs buffer. Non‐binding side‐chain steric bulk, the relative position of binding sites, and the scaffold size were all found to affect the ability of these receptors to discriminate between polyphosphate ions. Most receptors showed some selectivity for pyrophosphate over ATP and ADP in water and saline, and this selectivity was significantly enhanced in the biologically relevant Krebs buffer giving chemosensing ensembles capable of selective recognition of pyrophosphate in the presence of excess ATP.