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

The conformational study of a homogenous series of cyclic analogues of CCK 8 , selective for central receptors, such as Boc‐ X‐Tyr(SO 3 H)‐Nle‐ D ‐Lys ‐Trp‐Nle‐Asp‐Phe‐NH 2 , where X = L ‐Glu, D ‐Glu, or γ‐ D ‐Glu, was performed by 400‐MHz 1 H‐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 CCK 8 for both receptors types to be performed.