Carboxylic acids and tetrazoles as isosteric replacements for sulfate in cholecystokinin analogues.

A series of analogues of the satiety-inducing peptide cholecystokinin (CCK-8) was prepared in which the sulfated tyrosine required for activation of peripheral receptors was replaced with a carboxy(alkyl)- or tetrazolyl(alkyl)-phenylalanine to investigate whether an organic acid could serve the role of the sulfate group at the receptor. We conclude from this work that the requirement for a negative charge at the CCK-A receptor provided in the natural substrate by a sulfate group can be satisfied by organic acids