Design, synthesis, and biological evaluation of novel bifunctional C-terminal-modified peptides for delta/mu opioid receptor agonists and neurokinin-1 receptor antagonists.

Design, synthesis, and biological evaluation of novel bifunctional C-terminal-modified peptides for delta/mu opioid receptor agonists and neurokinin-1 receptor antagonists. Research Abstract Details 

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Design, synthesis, and biological evaluation of novel bifunctional C-terminal-modified peptides for delta/mu opioid receptor agonists and neurokinin-1 receptor antagonists. Abstract Text:

Takashi Yamamoto,Padma Nair,Peg Davis,Shou-wu Ma,Edita Navratilova,Sharif Moye,Suneeta Tumati,Josephine Lai,Todd W Vanderah,Henry I Yamamura,Frank Porreca,Victor J Hruby,

A series of bifunctional peptides that act as agonists for delta and mu opioid receptors with delta selectivity and as antagonist for neurokinin-1 (NK1) receptors were designed and synthesized for potential application as analgesics in various pain states. The peptides were characterized using radioligand binding assays and functional assays using cell membrane and animal tissue. Optimization was performed on the fifth residue which serves as an address moiety for both receptor recognitions. It had critical effects on both activities at delta/mu opioid receptors and NK1 receptors. Among the synthesized peptides, H-Tyr-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-O-3,5-Bzl(CF3) 2 (5) and H-Tyr-D-Ala-Gly-Phe-Nle-Pro-Leu-Trp-O-3,5-Bzl(CF3)2 (7) had excellent agonist activity for both delta opioid and mu opioid receptors and excellent antagonist activity for NK1 receptors. These results indicate that the rational design of multifunctional ligands with opioid agonist and neurokinin-1 antagonist activities can be accomplished and may provide a new tool for treatment of chronic and several pain states.

Design, synthesis, and biological evaluation of novel bifunctional C-terminal-modified peptides for delta/mu opioid receptor agonists and neurokinin-1 receptor antagonists. Publishing Authors By Initials

T Yamamoto,P Nair,P Davis,SW Ma,E Navratilova,S Moye,S Tumati,J Lai,TW Vanderah,HI Yamamura,F Porreca,VJ Hruby,

For similar urogenital system: genitalia: genitalia, male: vas deferens research abstracts see: urogenital system: genitalia: genitalia, male: vas deferens research

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Design, synthesis, and biological evaluation of novel bifunctional C-terminal-modified peptides for delta/mu opioid receptor agonists and neurokinin-1 receptor antagonists. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of medicinal chemistry

VOLUME: 50

Page Numbers: 2779-86

Journal Abbreviation: J. Med. Chem.

ISSN: 0022-2623

DAY: 22

MONTH: 05

YEAR: 2007

Design, synthesis, and biological evaluation of novel bifunctional C-terminal-modified peptides for delta/mu opioid receptor agonists and neurokinin-1 receptor antagonists. Information

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LANGUAGE: eng

NlmUniqueID: 9716531

Design, synthesis, and biological evaluation of novel bifunctional C-terminal-modified peptides for delta/mu opioid receptor agonists and neurokinin-1 receptor antagonists. Keywords Mesh Terms:

KEYWORDS: Vas Deferens

MESH TERMS: physiology

Chemical & Substance for Abstract: Design, synthesis, and biological evaluation of novel bifunctional C-terminal-modified peptides for delta/mu opioid receptor agonists and neurokinin-1 receptor antagonists. Information

Substance Name: tyrosyl-alanyl-glycyl-phenylalanyl-norle

Registry Number: 0

Grant and Affiliation Information for Design, synthesis, and biological evaluation of novel bifunctional C-terminal-modified peptides for delta/mu opioid receptor agonists and neurokinin-1 receptor antagonists.

AFFILIATION: Department of Chemistry, University of Arizona, Tucson, Arizona 85721, USA.

Country: United States

AGENCY: United States NIDA

GRANT: DA-13449

ACRONYM: DA

MEDLINETA: J Med Chem

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