Modification of the enkephalin "message" with an artificial polycationic C-terminus.
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.
Jacobson
A R
AR
Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106-7078.
Tam
S W
SW
Sayre
L M
LM
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002412:Cations; D004723:Endorphins / Q000737:chemistry; D004745:Enkephalins / Q000737:chemistry*; D006168:Guinea Pigs; D008297:Male; D008969:Molecular Sequence Data; D011869:Radioligand Assay
D002412:Cations; D004723:Endorphins; D004745:Enkephalins