Researcher:
David Muddiman, professor of chemistry, North Carolina State University, Raleigh
Project:
Profiling O-linked glycans as biomarkers in patients with ovarian cancer
Problem:
Developing the chemistry to efficiently cleave O-linked glycans from their peptides in complex biofluids.
Solution:
After a year of effort, Muddiman has finally figured out how to adapt a standard chemical process called beta-elimination to clip O-linked glycans from proteins in biological fluids ( J Proteome Res, in press). Following purification, he then analyzes these using high-end mass spectrometers to profile the glycans' molecular weights and abundances, and to collect structural data such as branching patterns and linkages.
The approach provides significant signal amplification over techniques such as glycan-specific gel staining (see sidebar), by concentrating the glycans. "If you have the same glycan on 100 proteins and you cleave it off, you get 100-fold amplification of the signal," Muddiman says. "But if it is stuck to 100 ...
