1. Degradation of proinsulin C-peptide in kidney and placenta extracts by a specific endoprotease activity.
- Author
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Melles E, Jörnvall H, Tryggvason S, Danielsson KG, Ekberg K, Tryggvason K, Wahren J, and Bergman T
- Subjects
- Amino Acid Sequence, Animals, Binding Sites, C-Peptide chemistry, Chromatography, High Pressure Liquid, Endopeptidases chemistry, Humans, Leucine chemistry, Mass Spectrometry, Mice, Molecular Sequence Data, Peptides chemistry, Protein Structure, Tertiary, Spectrometry, Mass, Electrospray Ionization, Time Factors, C-Peptide metabolism, Kidney metabolism, Placenta metabolism, Proinsulin chemistry
- Abstract
Degradation of proinsulin C-peptide in mouse kidney and human placenta extracts was studied using reverse-phase high-performance liquid chromatography and nano-electrospray mass spectrometry. In total, 15 proteolytic cleavage sites were identified in human and mouse C-peptides. Early sites included the peptide bonds N-terminal of Val/Leu10, Leu12, Leu21, Leu24 and Leu26 in different combinations for the two tissues and two peptides. Notably, these cleavages were N-terminal of a hydrophobic residue, and all but one N-terminal of Leu. A late degradation product of the human peptide detected in the kidney extract was the C-terminal hexapeptide, containing just one residue more than the biologically active C-terminal pentapeptide of C-peptide. We conclude that the degradation of C-peptide in kidney and placenta follows similar patterns, dominated by endopeptidase cleavages N-terminal of Leu.
- Published
- 2004
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