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.
Roy
P
P
Charpentier
B
B
Durieux
C
C
Dor
A
A
Roques
B P
BP
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism*; D006168:Guinea Pigs; D010179:Pancreas / Q000378:metabolism; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000378:metabolism*; D011487:Protein Conformation; D011949:Receptors, Cholecystokinin / Q000378:metabolism*
D010456:Peptides, Cyclic; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin