Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2006 Mar 9;49(5):1773-80.
doi: 10.1021/jm050851n.

Design and synthesis of novel hydrazide-linked bifunctional peptides as delta/mu opioid receptor agonists and CCK-1/CCK-2 receptor antagonists

Yeon Sun Lee  1 , Richard S Agnes, Hamid Badghisi, Peg Davis, Shou-wu Ma, Josephine Lai, Frank Porreca, Victor J Hruby
Affiliations

Design and synthesis of novel hydrazide-linked bifunctional peptides as delta/mu opioid receptor agonists and CCK-1/CCK-2 receptor antagonists

Yeon Sun Lee et al. J Med Chem. .

Abstract

A series of hydrazide-linked bifunctional peptides designed to act as agonists for delta/mu opioid receptors and antagonists for CCK-1/CCK-2 receptors was prepared and tested for binding to both opioid and CCK receptors and in functional assays. SAR studies in the CCK region examined the structural requirements for the side chain groups at positions 1', 2', and 4' and for the N-terminal protecting group, which are related to interactions not only with CCK, but also with opioid receptors. Most peptide ligands that showed high binding affinities (0.1-10 nM) for both delta and mu opioid receptors generally showed lower binding affinities (micromolar range) at CCK-1 and CCK-2 receptors, but were potent CCK receptor antagonists in the GPI/LMMP assay (up to Ke = 6.5 nM). The results indicate that it is reasonable to design chimeric bifunctional peptide ligands for different G-protein coupled receptors in a single molecule.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Design of hydrazide-linked bifunctional peptides.
Figure 2
Figure 2
Structure of hydrazide-linked bifunctional peptides synthesized in this study.
Figure 3
Figure 3
Synthesis of hydrazide-linked bifunctional peptides.
See this image and copyright information in PMC

References

    1. Wiesenfeld-Hallin Z, Lucas GA, Alster P, Xu XJ, Hokfelt T. Cholecystokinin/opioid interaction. Brain Res. 1999;848:78–89. - PubMed
    1. Itoh S, Katsuura G, Maeda Y. Caerulein and cholecystokinin suppress β-endomorphin-induced analgesia in the rat. Eur J Pharmacol. 1982;80:421–425. - PubMed
    1. Dickenson AH. Mechanisms of the analgesic actions of opiates and opioids. Br Med Bull. 1991;47:690–702. - PubMed
    1. Faris PL, Komisaruk BP, Watkins LR, Mayer DJ. Evidence for the neuropeptide cholecystokinin as an antagonist of opiate analgesia. Science. 1983;219:310–312. - PubMed
    1. Heinricher MM, Neubert MJ. Neural basis for the hyperalgesic action of cholecystokinin in the rostral ventromedial medulla. J Neurophysiol. 2004;92:1982–1989. - PubMed

Publication types

MeSH terms