Modification of the enkephalin "message" with an artificial polycationic C-terminus

Abstract

The C-terminal "address" sequences of prodynorphin-derived opioid peptides contain an unusually high proportion of basic residues, which are known to be crucial for conferring high activity and selectivity for kappa-opioid receptors. In an effort to investigate the possibility that the polycationic "tails" may be involved in a coulombic interaction with a complementary polyanionic receptor domain, we attached a series of achiral peptide-like cationic fragments to the C-terminus of the opioid peptide "message", Tyr-Gly-Gly-Phe. Binding of the various compounds to opioid receptor types in guinea pig brain membranes was weak, and the pharmacologic activities in the guinea pig ileum were marginal. These results indicate either that the chosen ligand design does not satisfy the structural requirements of the hypothesized coulombic interaction or that the latter is a minor criterion governing receptor recognition.

A Template Synthesis of Polyamine Macrocycles Containing the 1,1′-Bis(2-phenol) Function

“…The procedure shown in Scheme 1 was followed to obtain 5, whereas 1 and 2 were synthesized as previously reported. [18,19] The reaction of 1 with 2, carried out in chloroform solution, gives the imine derivative 3 as a yellow solid. The two imine functions were reduced with NaBH 4 in methanol to give 4 as a white solid after extraction of the crude solid mixture with CHCl 3 .…”