Microbial expression of Exendin-4 analog and its efficacy in mice model

Biologicals. 2017 Jul:48:82-91. doi: 10.1016/j.biologicals.2017.05.002. Epub 2017 May 26.

Abstract

Exendin-4 is a GLP 1 agonist incretin-mimetic peptide hormone comprising 39 amino acids. Exenatide (Byetta®) is a chemically synthesized version of Exendin-4 with an additional C-terminal amidation. Exenatide acts as a GLP-1 receptor agonist. This paper illustrates the method adopted for cloning, fermentation and purification of recombinant Exendin-4 analog expressed in Escherichia coli. The biologically expressed analog was extensively characterized using different orthogonal methods to confirm their biological activity and physicochemical properties. It was observed that the expressed analog showed comparable functional properties as that of Byetta® irrespective of their modes of development. Further, in vivo efficacy of the recombinant Exendin-4 analog was studied in Oral Glucose Tolerance Test (OGTT) in mice models. Byetta® and Exendin-4 analog treated groups showed comparable glucose lowering activity in the OGTT model.

Keywords: Diabetes mellitus; Exenatide; Exendin-4; Hyperglycemia; Insulin.

MeSH terms

  • Animals
  • Drug Evaluation, Preclinical
  • Escherichia coli*
  • Exenatide
  • Gene Expression*
  • Male
  • Mice
  • Peptides* / genetics
  • Peptides* / isolation & purification
  • Peptides* / pharmacology
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / pharmacology
  • Venoms* / biosynthesis
  • Venoms* / genetics
  • Venoms* / isolation & purification
  • Venoms* / pharmacology

Substances

  • Peptides
  • Recombinant Proteins
  • Venoms
  • Exenatide