Synthesis of the IGF-II-like hormone vesiculin using regioselective formation of disulfide bonds

Org Biomol Chem. 2013 May 21;11(19):3145-50. doi: 10.1039/c3ob40322j. Epub 2013 Mar 28.

Abstract

Diabetes mellitus, characterised by hyperglycemia and altered β-cell function, is an increasingly common disorder affecting millions of individuals world-wide. While therapeutic regimens exist to manage the condition, diabetic individuals remain prone to complications that are detrimental to both their length and quality of life. An improved understanding of the disease which may then enable development of new treatments is therefore a desirable goal. Vesiculin, a novel IGF-II-like protein was recently isolated from the secretory granules of murine β-cells, and preliminary studies indicate it is capable of signalling via the insulin receptor (IR)/insulin-like growth factor receptor 1(IGF1R) family giving it the potential to elicit both metabolic and mitogenic responses in the beta-cell. In order to facilitate further studies on this new member of the insulin-family of hormones, we undertook a chemical synthesis of the protein using regioselective disulfide bond formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disulfides / chemical synthesis*
  • Disulfides / chemistry
  • Dose-Response Relationship, Drug
  • Glycogen / biosynthesis
  • Glycogen / chemistry
  • Insulin-Like Growth Factor II / chemistry*
  • Male
  • Mice
  • Muscle Fibers, Skeletal / chemistry
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism
  • Nerve Tissue Proteins / chemical synthesis*
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Disulfides
  • Nerve Tissue Proteins
  • vesiculin
  • Insulin-Like Growth Factor II
  • Glycogen