Copper(II) Affects the Biochemical Behavior of Proinsulin C-peptide by Forming Ternary Complexes with Serum Albumin

• DOI: 10.1021/jacs.3c04599
• Publication Date: 2023-07-24T17:48:41Z
• Authors: Jessica A. San Juan; Khetpakorn Chakar...; Zhecheng He; Rebeca L. Fernandez; Michael J. Stevenson; Nathaniel H. O. H...; Samuel E. Janisse; Lee-Ping Wang; R. David Britt; Marie C. Heffern
• Keywords: Proinsulin; C-peptide

Peptide hormones are essential signaling molecules with therapeutic importance. Identifying regulatory factors that drive their activity gives important insight into mode of action and clinical development. In this work, we demonstrate the combined impact Cu(II) serum protein albumin on C-peptide, a 31-mer peptide derived from same prohormone as insulin. C-peptide exhibits beneficial effects, particularly in diabetic patients, but its use has been hampered by lack mechanistic understanding. We show mediates formation ternary complexes between resulting species depend order addition. These notably alter activity, showing differences or Cu(II)/peptide alone redox protection well cellular internalization peptide. standard immunoassays for measuring levels, inflate quantitation peptide, suggesting such adducts may affect biomarker quantitation. Altogether, our work points to potential relevance Cu(II)-linked C-peptide/albumin peptide's mechanism application biomarker.