Conformational behavior of cyclic CCK-related peptides determined by 400-MHz 1H-NMR: relationships with affinity and selectivity for brain receptors.

The conformational study of a homogenous series of cyclic analogues of CCK8, selective for central receptors, such as Boc-X-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2, where X = L-Glu, D-Glu, or gamma-D-Glu, was performed by 400-MHz 1H-nmr. The regular increase in affinity for central receptors when going from [L-Glu] to [gamma-D-Glu] is correlated to (a) an enhancement in internal flexibility of the cyclic moiety, (b) an external orientation of the tyrosine side chain, and (c) a restructuring of the C-terminal part of the peptide. All these results could permit a modeling of biologically active conformation of CCK8 for both receptors types to be performed.