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; F. Porreca; Victor J. Hruby

doi:10.1016/S0960-894X(00)80675-7

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
, F. Porreca
, Victor J. Hruby

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

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 language	English (US)
Pages (from-to)	831-834
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	3
Issue number	5
DOIs	https://doi.org/10.1016/S0960-894X(00)80675-7
State	Published - May 1993

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

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

Cite this

Hristova-Kazmierski, M. K., Horan, P., Davis, P., Yamamura, H. I., Kramer, T., Horvath, R., Kazmierski, W. M., Porreca, F., & Hruby, V. J. (1993). A new approach to enhance bioavailability of biologically active peptides: conjugation of a δ opioid agonist to β-cyclodextrin. Bioorganic and Medicinal Chemistry Letters, 3(5), 831-834. https://doi.org/10.1016/S0960-894X(00)80675-7

Hristova-Kazmierski, MK, Horan, P, Davis, P, Yamamura, HI, Kramer, T, Horvath, R, Kazmierski, WM, Porreca, F & Hruby, VJ 1993, 'A new approach to enhance bioavailability of biologically active peptides: conjugation of a δ opioid agonist to β-cyclodextrin', Bioorganic and Medicinal Chemistry Letters, vol. 3, no. 5, pp. 831-834. https://doi.org/10.1016/S0960-894X(00)80675-7

@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 F. Porreca and Hruby, \{Victor J.\}",

year = "1993",

month = may,

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 Ltd",

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, F.

AU - Hruby, Victor J.

PY - 1993/5

Y1 - 1993/5

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 - https://www.scopus.com/pages/publications/0027191259

UR - https://www.scopus.com/pages/publications/0027191259#tab=citedBy

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

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

M3 - Article

AN - SCOPUS:0027191259

SN - 0960-894X

VL - 3

SP - 831

EP - 834

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 5

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this