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Analysis of Metal Effects on C‐Peptide Structure and Internalization
Author(s) -
Stevenson Michael J.,
Farran Ian C.,
Uyeda Kylie S.,
San Juan Jessica A.,
Heffern Marie C.
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900172
Subject(s) - internalization , peptide , chemistry , biophysics , function (biology) , intracellular , biochemistry , microbiology and biotechnology , receptor , biology
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 Cr III , Cu II , and Zn II 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.