A NEW APPROACH TO ENHANCE BIOAVAILABILITY OF BIOLOGICALLY-ACTIVE PEPTIDES - CONJUGATION OF A DELTA-OPIOID AGONIST TO BETA-CYCLODEXTRIN

Authors
HRISTOVAKAZMIERSKI MK HORAN P DAVIS P YAMAMURA HI KRAMER T HORVATH R KAZMIERSKI WM PORRECA F HRUBY VJ
Citation
Mk. Hristovakazmierski et al., A NEW APPROACH TO ENHANCE BIOAVAILABILITY OF BIOLOGICALLY-ACTIVE PEPTIDES - CONJUGATION OF A DELTA-OPIOID AGONIST TO BETA-CYCLODEXTRIN, Bioorganic & medicinal chemistry letters, 3(5), 1993, pp. 831-834
Citations number
8
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
3
Issue
5
Year of publication
1993
Pages
831 - 834
Database
ISI
SICI code
0960-894X(1993)3:5<831:ANATEB>2.0.ZU;2-I
Abstract
The cyclic delta opioid agonist [p-I-Phe4]DPDPE, 1, was conjugated to mono-6-amino-permethyl-beta-cyclodextrin at the C-terminus to improve the bioavailability of 1. In the rat brain binding assay, the conjugat e 8 showed an IC50 = 134 nM vs. a delta ligand and IC50 > 10 muM at th e mu receptor, making it less potent and selective than 1. However, 8 shows antinociceptive properties (i.v.) in the mouse tail flick test a nd prolonged activity.