A Cyclic CCK8 Analogue Selective for the Cholecystokinin Type A Receptor: Design, Synthesis, NMR Structure and Binding Measurements (pages 1176–1187)
Stefania De Luca, Raffaele Ragone, Chiara Bracco, Giuseppe Digilio, Luigi Aloj, Diego Tesauro, Michele Saviano, Carlo Pedone and Giancarlo Morelli
Version of Record online: 3 NOV 2003 | DOI: 10.1002/cbic.200300635
Designer peptides: A cyclic CCK8 analogue, cyclo29,34[Dpr29,Lys34]-CCK8 (Dpr=L-2,3-diaminopropionic acid), has been designed on the basis of the complex between the N-terminal fragment of the CCKA receptor and its natural ligand CCK8. The conformational features of cyclo29,34[Dpr29,Lys34]-CCK8 have been determined in aqueous solution and in water containing DPC-d38 micelles. The binding properties of cyclo29,34[Dpr29,Lys34]-CCK8 to the N-terminal receptor fragment (see model) have been investigated in a micellar environment. Estimates of the apparent dissociation constant were in the range of 70–150 nM. Preliminary in vivo studies have been performed with cell lines transfected with the CCKA receptor. Picture = structure of analogue (stick/space filled) and receptor (ribbon).