C-peptide, a biological molecule co-released with active insulin from the pancreas, is of emerging interest for its beneficial hormonal-like activities. Initially thought to be inert, it is now well-accepted that C-peptide demonstrates therapeutic drug promise in ameliorating diabetes-related disorders such as kidney dysfunction and vascular neuropathies. However, the mechanisms behind the peptide remain unclear. A molecular understanding of C-peptide structure and stability in the bloodstream is necessary to build a better foundation of how the peptide elicits its beneficial effects. Our previous work has shown that micronutrient metals, such as copper, can directly bind to C-peptide and alter its cellular internalization. Because metals can influence C-peptide’s mode of action, the next step is to determine how metal/C-peptide structure can influence peptide stability. Albumin is one of the most abundant serum protein chaperones in the bloodstream and is a major constituent for exchangeable copper pool in blood plasma. Because of this, ternary complexation may form between C-peptide, serum albumin, and copper. To determine the role serum albumin and copper may have on C-peptide's activity, various spectroscopic techniques such as CD, UV-Vis, and fluorescence were used, as well as immunofluorescence. Direct changes in peptide binding and cellular internalization displayed a specific ternary schematic between C-peptide, serum albumin, and copper. Overall, serum albumin could be the key to a better understanding of how the peptide induces its physiological effects, which can aid C-peptide formulation.

Investigating the role of copper in mediating interactions between proinsulin C-peptide and serum albumin

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.