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 journalArticle

35 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)367-372
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number2
DOIs
StatePublished - Jan 15 2006

Fingerprint

Bioactivity
Cysteine
Enkephalins
Sulfhydryl Compounds
Disulfides
Alanine
Opioid Analgesics
Peptides
biphalin
tyrosyl-alanyl-glycyl-phenylalanine

Keywords

  • Biphalin
  • Cyclic peptides

ASJC Scopus subject areas

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

Cite this

Synthesis and biological activity of the first cyclic biphalin analogues. / Mollica, Adriano; Davis, Peg; Ma, Shou Wu; Porreca, Frank; Lai, Josephine; Hruby, Victor J.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 16, No. 2, 15.01.2006, p. 367-372.

Research output: Contribution to journalArticle

Mollica, Adriano ; Davis, Peg ; Ma, Shou Wu ; Porreca, Frank ; Lai, Josephine ; Hruby, Victor J. / Synthesis and biological activity of the first cyclic biphalin analogues. In: Bioorganic and Medicinal Chemistry Letters. 2006 ; Vol. 16, No. 2. pp. 367-372.
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