Forskning ved Københavns Universitet - Københavns Universitet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

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.
OriginalsprogEngelsk
TidsskriftJournal of Proteome Research
Vol/bind9
Udgave nummer10
Sider (fra-til)5250-5261
Antal sider12
ISSN1535-3893
DOI
StatusUdgivet - 2010

ID: 23207812