Details

Autor(en) / Beteiligte

• Blixt, Ola
• Cló, Emiliano
• Nudelman, Aaron S
• Sørensen, Kasper Kildegaard
• Clausen, Thomas
• Wandall, Hans H
• Livingston, Philip O
• Clausen, Henrik
• Jensen, Knud J

Titel

A High-Throughput O-Glycopeptide Discovery Platform for Seromic Profiling

Ist Teil von

• Journal of proteome research, 2010-10, Vol.9 (10), p.5250-5261

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.