Synthesis and biological activity of the first cyclic biphalin analogues

Adriano Mollica; Peg Davis; Shou Wu Ma; Frank Porreca; Josephine Lai; Victor J. Hruby

doi:10.1016/j.bmcl.2005.09.080

Synthesis and biological activity of the first cyclic biphalin analogues

Adriano Mollica, Peg Davis, Shou Wu Ma, Frank Porreca, Josephine Lai, Victor J. Hruby

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

43 Scopus citations

Abstract

Biphalin is a linear octapeptide with strong opioid activity. Its structure is based on two identical sequences derived from enkephalins joined C-terminal to C-terminal by an hydrazide bridge (Tyr-D-Ala-Gly-Phe-NH-NH ← Phe ← Gly ← D-Ala ← Tyr). In this study we present the design, synthesis, and biological evaluation of the first cyclic biphalin analogues. d-Alanine residues in positions 2, 2′ of the parent peptide were replaced by d- and l-cysteine and an intramolecular disulfide bond between the cysteine thiol groups was introduced. We obtained two cyclic analogues with quite different biological profiles.

Original language	English (US)
Pages (from-to)	367-372
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	2
DOIs	https://doi.org/10.1016/j.bmcl.2005.09.080
State	Published - Jan 15 2006

Keywords

Biphalin
Cyclic peptides

ASJC Scopus subject areas

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

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10.1016/j.bmcl.2005.09.080

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title = "Synthesis and biological activity of the first cyclic biphalin analogues",

abstract = "Biphalin is a linear octapeptide with strong opioid activity. Its structure is based on two identical sequences derived from enkephalins joined C-terminal to C-terminal by an hydrazide bridge (Tyr-D-Ala-Gly-Phe-NH-NH ← Phe ← Gly ← D-Ala ← Tyr). In this study we present the design, synthesis, and biological evaluation of the first cyclic biphalin analogues. d-Alanine residues in positions 2, 2′ of the parent peptide were replaced by d- and l-cysteine and an intramolecular disulfide bond between the cysteine thiol groups was introduced. We obtained two cyclic analogues with quite different biological profiles.",

keywords = "Biphalin, Cyclic peptides",

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T1 - Synthesis and biological activity of the first cyclic biphalin analogues

AU - Mollica, Adriano

AU - Davis, Peg

AU - Ma, Shou Wu

AU - Porreca, Frank

AU - Lai, Josephine

AU - Hruby, Victor J.

N1 - Funding Information: This work was supported by a grant from the U.S., Public Health Service, National Institute of Drug Abuse, DA 06284.

PY - 2006/1/15

Y1 - 2006/1/15

N2 - Biphalin is a linear octapeptide with strong opioid activity. Its structure is based on two identical sequences derived from enkephalins joined C-terminal to C-terminal by an hydrazide bridge (Tyr-D-Ala-Gly-Phe-NH-NH ← Phe ← Gly ← D-Ala ← Tyr). In this study we present the design, synthesis, and biological evaluation of the first cyclic biphalin analogues. d-Alanine residues in positions 2, 2′ of the parent peptide were replaced by d- and l-cysteine and an intramolecular disulfide bond between the cysteine thiol groups was introduced. We obtained two cyclic analogues with quite different biological profiles.

AB - Biphalin is a linear octapeptide with strong opioid activity. Its structure is based on two identical sequences derived from enkephalins joined C-terminal to C-terminal by an hydrazide bridge (Tyr-D-Ala-Gly-Phe-NH-NH ← Phe ← Gly ← D-Ala ← Tyr). In this study we present the design, synthesis, and biological evaluation of the first cyclic biphalin analogues. d-Alanine residues in positions 2, 2′ of the parent peptide were replaced by d- and l-cysteine and an intramolecular disulfide bond between the cysteine thiol groups was introduced. We obtained two cyclic analogues with quite different biological profiles.

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KW - Cyclic peptides

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Synthesis and biological activity of the first cyclic biphalin analogues

Abstract

Keywords

ASJC Scopus subject areas

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