Synthesis and cystine/cysteine-catalyzed oxidative folding of the amaranth α-amylase inhibitor

Valentin Lozanov, Corrado Guarnaccia, András Patthy, Salvatore Foti, Sándor Pongor

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

We report here the total synthesis of the α-amylase inhibitor (AAI), a 32-residue-long peptide with three disulfide bridges, isolated from amaranth seeds (Chagolla-Lopez, A., Blanco-Labra, A., Patthy, A. Sanchez, R. and Pongor S. (1994) J. Biol. Chem. 269, 23675-23680). The synthesis was carded out using a stepwise solid-phase approach based on the Fmoc/t-Bu chemistry, combined with the S-acetamidomethyl protection for cysteines. The linear, reduced peptide was obtained after two reduction steps, using 1,4-dithio-DL- threitol and tri(2-carboxyethyl)phosphine hydrochloride in basic and acidic conditions, respectively. Disulfide bridges were formed by oxidative folding in a cystine/cysteine redox buffer, these conditions were found superior to air oxidation and to glutathione-catalyzed oxidative folding. The physicochemical and enzyme inhibitory properties of synthetic AAI were found identical with those of the natural product. Several orthogonal protection schemes proved unsuccessful in obtaining a biologically active product.

Original languageEnglish
Pages (from-to)65-72
Number of pages8
JournalJournal of Peptide Research
Volume50
Issue number1
DOIs
Publication statusPublished - Jan 1 1997

Keywords

  • Cystine/cysteine
  • Disulfide bond
  • Glutathione
  • Oxidative folding
  • Solid-phase peptide synthesis
  • α-amylase inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

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