A new approach to enhance bioavailability of biologically active peptides

conjugation of a δ opioid agonist to β-cyclodextrin

Maria K. Hristova-Kazmierski, P. Horan, P. Davis, H. I. Yamamura, T. Kramer, R. Horvath, W. M. Kazmierski, Frank Porreca, Victor J Hruby

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The cyclic δ opioid against [p-I-Phe4]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 IC50 = 134 nM vs. a δ ligand and IC50 > 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.

Original languageEnglish (US)
Pages (from-to)831-834
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume3
Issue number5
DOIs
StatePublished - 1993

Fingerprint

D-Penicillamine (2,5)-Enkephalin
Cyclodextrins
Opioid Analgesics
Biological Availability
Inhibitory Concentration 50
Rats
Assays
Brain
Ligands
Peptides
Tail

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

A new approach to enhance bioavailability of biologically active peptides : conjugation of a δ opioid agonist to β-cyclodextrin. / Hristova-Kazmierski, Maria K.; Horan, P.; Davis, P.; Yamamura, H. I.; Kramer, T.; Horvath, R.; Kazmierski, W. M.; Porreca, Frank; Hruby, Victor J.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 3, No. 5, 1993, p. 831-834.

Research output: Contribution to journalArticle

Hristova-Kazmierski, Maria K. ; Horan, P. ; Davis, P. ; Yamamura, H. I. ; Kramer, T. ; Horvath, R. ; Kazmierski, W. M. ; Porreca, Frank ; Hruby, Victor J. / A new approach to enhance bioavailability of biologically active peptides : conjugation of a δ opioid agonist to β-cyclodextrin. In: Bioorganic and Medicinal Chemistry Letters. 1993 ; Vol. 3, No. 5. pp. 831-834.
@article{6dfd33db7bbf4047a22904ed337d173d,
title = "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-Phe4]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 IC50 = 134 nM vs. a δ ligand and IC50 > 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.",
author = "Hristova-Kazmierski, {Maria K.} and P. Horan and P. Davis and Yamamura, {H. I.} and T. Kramer and R. Horvath and Kazmierski, {W. M.} and Frank Porreca and Hruby, {Victor J}",
year = "1993",
doi = "10.1016/S0960-894X(00)80675-7",
language = "English (US)",
volume = "3",
pages = "831--834",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "5",

}

TY - JOUR

T1 - A new approach to enhance bioavailability of biologically active peptides

T2 - conjugation of a δ opioid agonist to β-cyclodextrin

AU - Hristova-Kazmierski, Maria K.

AU - Horan, P.

AU - Davis, P.

AU - Yamamura, H. I.

AU - Kramer, T.

AU - Horvath, R.

AU - Kazmierski, W. M.

AU - Porreca, Frank

AU - Hruby, Victor J

PY - 1993

Y1 - 1993

N2 - The cyclic δ opioid against [p-I-Phe4]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 IC50 = 134 nM vs. a δ ligand and IC50 > 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.

AB - The cyclic δ opioid against [p-I-Phe4]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 IC50 = 134 nM vs. a δ ligand and IC50 > 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.

UR - http://www.scopus.com/inward/record.url?scp=0027191259&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027191259&partnerID=8YFLogxK

U2 - 10.1016/S0960-894X(00)80675-7

DO - 10.1016/S0960-894X(00)80675-7

M3 - Article

VL - 3

SP - 831

EP - 834

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 5

ER -