A high-throughput O-glycopeptide discovery platform for seromic profiling

Research output: Contribution to journalJournal articleResearchpeer-review

Biomarker microarrays are becoming valuable tools for serological screening of disease-associated autoantibodies. Post-translational modifications (PTMs) such as glycosylation extend the range of protein function, and a variety of glycosylated proteins are known to be altered in disease progression. Here, we have developed a synthetic screening microarray platform for facile display of O-glycosylated peptides (O-PTMs). By introduction of a capping step during chemical solid-phase glycopeptide synthesis, selective enrichment of N-terminal glycopeptide end products was achieved on an amine-reactive hydrogel-coated microarray glass surface, allowing high-throughput display of large numbers of glycopeptides. Utilizing a repertoire of recombinant glycosyltransferases enabled further diversification of the array libraries in situ and display of a new level of potential biomarker candidates for serological screening. As proof-of-concept, we have demonstrated that MUC1 glycopeptides could be assembled and used to detect autoantibodies in vaccine-induced disease-free breast cancer patients and in patients with confirmed disease at time of diagnosis.
Original languageEnglish
JournalJournal of Proteome Research
Volume9
Issue number10
Pages (from-to)5250-5261
Number of pages12
ISSN1535-3893
DOIs
Publication statusPublished - 2010

Bibliographical note

Keywords: Autoantibodies; Breast Neoplasms; Cancer Vaccines; Female; Glycopeptides; Glycosylation; Glycosyltransferases; Humans; Mucin-1; Peptides; Proteomics; Tumor Markers, Biological

ID: 23207812