A new approach to enhance bioavailability of biologically active peptides: conjugation of a δ opioid agonist to β-cyclodextrin

Abstract The cyclic δ opioid against [p-I-Phe 4 ]DPDPE, 1 , was conjugated to mono-6-amino-permethyl-β-cyclodextrin at the C-terminus to improve the bioavailability of 1 . In the rat brain building assay, the conjugate 8 showed an IC 50 = 134 nM vs. a δ ligand and IC 50 > 10 μM at the μ receptor, making it less potent and selective than 1 . However, 8 shows antinociceptive properties (i.v.) in the mouse tail flick test and prolonged activity.