Analysis of Metal Effects on C-Peptide Structure and Internalization

Michael J. Stevenson, Ian C. Farran, Kylie S. Uyeda, Jessica A. San Juan, Marie Heffern

Research output: Contribution to journalArticle

Abstract

The connecting peptide (C-peptide) has received increased attention for its potential therapeutic effects in ameliorating illnesses such as kidney disease and diabetes. Although the mechanism of C-peptide signaling remains elusive, evidence supports its internalization and intracellular function. Emerging research is uncovering the diverse biological roles metals play in controlling and affecting the function of bioactive peptides. The work presented herein investigates interactions between C-peptide and first-row d-block transition metals, as well as their effects on C-peptide internalization into cells. Through spectroscopic techniques, it is demonstrated that CrIII, CuII, and ZnII bind to C-peptide with differing stoichiometries and biologically relevant affinities. In addition, metal binding elicits both subtle changes in secondary structure and inhibits adoption of an α-helical character in environments where the dielectric constants are reduced. This study shows how metal ions can modulate peptide hormone activity through subtle structural changes to disrupt cellular uptake.

Original languageEnglish (US)
JournalChemBioChem
DOIs
StateAccepted/In press - Jan 1 2019

Keywords

  • C-peptides
  • charge transfer
  • fluorescence
  • hormones
  • transition metals

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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  • Cite this

    Stevenson, M. J., Farran, I. C., Uyeda, K. S., San Juan, J. A., & Heffern, M. (Accepted/In press). Analysis of Metal Effects on C-Peptide Structure and Internalization. ChemBioChem. https://doi.org/10.1002/cbic.201900172