Synthesis and solution characterization of a porphyrin-CCK8 conjugate

In this paper we report the synthesis and a detailed NMR solution characterization 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 through an amide bond to the side chain of a Lys residue introduced at the N-terminus of CCK8. A molecular dynamics simulation, based on the NMR structure of the complex between CCK8 and the N-terminal extracellular arm of the CCKA receptor, is also reported. Both the NMR study and the molecular dynamics simulation indicate that the porphyrin-peptide conjugate might be able to bind to the CCKA receptor model. The results of the molecular dynamics calculations show that the conformational features of the CCK8/CCKA receptor model complex and of the PK-CCK8/CCKA receptor-model complex are similar. This evidence supports the view that the introduction of the porphyrin-Lys moiety does not influence the mode of ligand binding to the CCKA receptor model. 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. Moreover, the absence of NOE contacts between the porphyrin and the peptide indicates that the macrocyclic ring is directed away from the peptide region involved in the binding with the receptor. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd.