Open AccessEnrichment of Collagen Fragments Using Dimeric Collagen Hybridizing Peptide for Urinary Collagenomics
Author(s) -
Julian Kessler,
Yang Li,
Jaime Fornetti,
Alana L. Welm,
S. Michael Yu
Publication year - 2020
Publication title -
journal of proteome research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.644
H-Index - 161
eISSN - 1535-3907
pISSN - 1535-3893
DOI - 10.1021/acs.jproteome.0c00055
Subject(s) - peptide , biomarker discovery , type i collagen , biomarker , chemistry , microbiology and biotechnology , collagen, type i, alpha 1 , biology , computational biology , proteomics , biochemistry , gene , extracellular matrix , endocrinology
Collagen remodeling in normal and pathologic conditions releases numerous collagen fragments into biological fluids. Although a few collagen fragments have been tested as biomarkers for disease indication, most occur at trace levels, making them nearly impossible to detect even with modern analytical tools. Here we report a new way to enrich collagen fragments that allows complete peptidomic analysis of collagen fragments in urine. Enrichment is made possible by dimeric collagen hybridizing peptides (CHPs) that bind collagen fragments originating from the triple helical regions of all collagen types with minimal sequence bias. LC-MS/MS analysis of enriched mouse urine revealed an average of 383 collagenous peptide fragments per sample (compared to 34 for unenriched sample), which could be mapped to all types of mouse collagens in the SwissProt database including FACITs and MACITs. Hierarchical clustering of a selected panel of the detected fragments separated osteopenic mice from healthy mice. The results demonstrate dimeric CHP's ability to enrich collagen fragments from biological fluid and its potential to aid peptidomics-based disease detection and biomarker discovery.