Copper(II) Affects the Biochemical Behavior of Proinsulin C-peptide by Forming Ternary Complexes with Serum Albumin
Issued Date
2023-08-02
Resource Type
ISSN
00027863
eISSN
15205126
Scopus ID
2-s2.0-85166391910
Pubmed ID
37486968
Journal Title
Journal of the American Chemical Society
Volume
145
Issue
30
Start Page
16726
End Page
16738
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of the American Chemical Society Vol.145 No.30 (2023) , 16726-16738
Suggested Citation
San Juan J.A., Chakarawet K., He Z., Fernandez R.L., Stevenson M.J., Harder N.H.O., Janisse S.E., Wang L.P., Britt R.D., Heffern M.C. Copper(II) Affects the Biochemical Behavior of Proinsulin C-peptide by Forming Ternary Complexes with Serum Albumin. Journal of the American Chemical Society Vol.145 No.30 (2023) , 16726-16738. 16738. doi:10.1021/jacs.3c04599 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/95521
Title
Copper(II) Affects the Biochemical Behavior of Proinsulin C-peptide by Forming Ternary Complexes with Serum Albumin
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Abstract
Peptide hormones are essential signaling molecules with therapeutic importance. Identifying regulatory factors that drive their activity gives important insight into their mode of action and clinical development. In this work, we demonstrate the combined impact of Cu(II) and the serum protein albumin on the activity of C-peptide, a 31-mer peptide derived from the same prohormone as insulin. C-peptide exhibits beneficial effects, particularly in diabetic patients, but its clinical use has been hampered by a lack of mechanistic understanding. We show that Cu(II) mediates the formation of ternary complexes between albumin and C-peptide and that the resulting species depend on the order of addition. These ternary complexes notably alter peptide activity, showing differences from the peptide or Cu(II)/peptide complexes alone in redox protection as well as in cellular internalization of the peptide. In standard clinical immunoassays for measuring C-peptide levels, the complexes inflate the quantitation of the peptide, suggesting that such adducts may affect biomarker quantitation. Altogether, our work points to the potential relevance of Cu(II)-linked C-peptide/albumin complexes in the peptide’s mechanism of action and application as a biomarker.