Synthesis of Carboxyl-Terminal Extension Analogs of Dermorphin and Evaluation of Their Opioid Receptor-Binding and Opioid Activities.

Abstract
Eight dermorphin (DM) analogs extended at the C-terminus, based on the sequence of prepro-DM deduced from the cDNA, were synthesized by a simultaneous solid-phase method in which a pair of peptides was synthesized in a single vessel. Six peptides (three pairs) were obtained in satisfactory yields (17-37%). In the opioid receptor-binding assay using a rat brain homogenate, the mu-affinities correlated well to the net positive charges of peptides, and DM-Gly-Glu-Ala-Lys-Lys-Ile-Lys-Arg-NH2 showed the highest mu-affinity, 115-fold that of DM. But, in the guinea pig ileum assay, extension analogs with net positive charge of 2 to 4 exhibited potencies comparable to or slightly lower than that of DM, even though they possessed 2- to 115-fold higher mu-affinities than DM in the receptor-binding assay.

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