Conformational behavior of cyclic CCK‐related peptides determined by 400‐MHz 1H‐nmr: Relationships with affinity and selectivity for brain receptors

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Abstract
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 γ‐D‐Glu, was performed by 400‐MHz 1H‐nmr. The regular increase in affinity for central receptors when going from [L‐Glu] to [γ‐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.