Preparation and properties of glucagon analogs prepared by semi-synthesis from CNBr-glucagon

David E. Wright, Victor J. Hruby, Martin Rodbell

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The semi-synthetic approach has been used to obtain new analogs of the peptide hormone glucagon. Using the highly purified 27 amino acid fragment of cyanogen bromide-treated glucagon, we have prepared, by nucleophilic addition to the lactone ring, the following derivatives: CNBr-Gly28-glucagon, CNBr-glucagon hydrazide, CNBr-glucagon n-butylamide and CNBr-glucagon biotinamide. Direct aminolysis of the lactone was successful only with sterically unhindered primary amines. Addition of an amino acid could be accomplished by formation of the peptide hydrazide followed by azide coupling. All these analogs were full agonists with decreased potency relative to the native hormone. Examination of the structure-function relationships of these new C-terminal glucagon derivatives suggests that the hydrophobic side-chain of methionine is important to the binding of glucagon to its receptor and that the C-terminal portion of glucagon is only involved in the binding of the hormone to the receptor and not in the transduction process.

Original languageEnglish (US)
Pages (from-to)49-58
Number of pages10
JournalBiochimica et Biophysica Acta - General Subjects
Volume631
Issue number1
DOIs
StatePublished - Jan 1 1980

Keywords

  • (des-Asn, Thr) (6-aminohexyl homoserineamide biotinamide )-glucagon
  • (des-Asn, Thr) (Hse, Gly)-glucagon
  • (des-Asn, Thr) (homoserine n-butylamide)-glucagon
  • (des-Asn, Thr) (homoserineamide)-glucagon
  • (des-Asn, Thr) (homoserinelactone)-glucagon
  • Adenylate cyclase
  • Boc
  • Bu
  • CNBr-Gly-glucagon
  • CNBr-glucagon
  • CNBr-glucagon diaminohexylbiotinamide
  • CNBr-glucagon hydrazide
  • CNBr-glucagon n-butylamide
  • Glucagon analog
  • N-hydroxysuccinimide
  • NPS
  • OSu
  • Semi-synthesis
  • TFA
  • nitrophenylsulfenyl
  • t-butyl
  • t-butyloxycarbonyl
  • trifluoroacetate

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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