A high-throughput O-glycopeptide discovery platform for seromic profiling
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
A high-throughput O-glycopeptide discovery platform for seromic profiling. / Blixt, Ola; Cló, Emiliano; Nudelman, Aaron Samuel; Sørensen, Kasper Kildegaard; Clausen, Thomas; Wandall, Hans H.; Livingston, Philip O.; Clausen, Henrik; Jensen, Knud Jørgen.
In: Journal of Proteome Research, Vol. 9, No. 10, 2010, p. 5250-5261.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - A high-throughput O-glycopeptide discovery platform for seromic profiling
AU - Blixt, Ola
AU - Cló, Emiliano
AU - Nudelman, Aaron Samuel
AU - Sørensen, Kasper Kildegaard
AU - Clausen, Thomas
AU - Wandall, Hans H.
AU - Livingston, Philip O.
AU - Clausen, Henrik
AU - Jensen, Knud Jørgen
N1 - Keywords: Autoantibodies; Breast Neoplasms; Cancer Vaccines; Female; Glycopeptides; Glycosylation; Glycosyltransferases; Humans; Mucin-1; Peptides; Proteomics; Tumor Markers, Biological
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
U2 - 10.1021/pr1005229
DO - 10.1021/pr1005229
M3 - Journal article
C2 - 20726594
VL - 9
SP - 5250
EP - 5261
JO - Journal of Proteome Research
JF - Journal of Proteome Research
SN - 1535-3893
IS - 10
ER -
ID: 23207812