Synthesis and solution characterization of a porphyrin-CCK8 conjugate

In this paper we report the synthesis and a detailed NMR solution character ization of a new CCK8 analogue and its indium(III) complex, PK-CCK8 and In- PK-CCK8. The new compounds contain a porphyrin moiety covalently bound thro ugh an amide bond to the side chain of a Lys residue introduced at the IV-t erminus of CCK8. A molecular dynamics simulation, based on the NMR structur e of the complex between CCK8 and the N-terminal extracellular arm of the C CKA receptor, is also reported. Both the NMR study and the molecular dynami cs simulation indicate that the porphyrin-peptide conjugate might be able t o bind to the CCKA receptor model. The results of the molecular dynamics ca lculations show that the conformational features of the CCK8/CCKA receptor model complex and of the PK-CCK8/CCKA receptor-model complex are similar. T his evidence supports the view that the introduction of the porphyrin-Lys m oiety does not influence the mode of ligand binding to the CCKA receptor mo del. The NMR structure of PK-CCK8 in DMSO consists of a well defined pseudo -helical N-terminal region, while the C-terminal region is flexible. Moreov er, the absence of NOE contacts between the porphyrin and the peptide indic ates that the macrocyclic ring is directed away from the peptide region inv olved in the binding with the receptor. Copyright (C) 2001 European Peptide Society and John Wiley & Sons, Ltd.