ChemiCALScience and Engineering
News
College of Chemistry
2003 News Index
Detection of Modified Sugar Proteins: Bertozzi
from Chemical and Engineering News
A
rapid and efficient chemical strategy has been developed to identify
proteins with a mysterious modification--the attachment of oxygen-linked
-N-acetylglucosamine (O-GlcNAc) sugars.
O-GlcNAc modification occurs widely on proteins in the nucleus
and cytoplasm of multicellular plants and animals. The function
of this glycosylation process is poorly understood, but it may
play a key role in transcription, cytoskeletal organization, and
signaling, and O-GlcNAc metabolism may be abnormally regulated
in diabetes.
Tools have been developed recently to aid identification of O-GlcNAc-modified
proteins, including site-specific antibodies and a liquid chromatography-tandem
mass spectrometry technique. Now, chemistry professor Carolyn
R. Bertozzi of Howard Hughes Medical Institute and the University
of California, Berkeley, postdoctoral fellow David J. Vocadlo,
and coworkers have devised a complementary approach that may prove
more useful for high-throughput proteomics applications [Proc.
Natl. Acad. Sci. USA, published online July 21, http://www.pnas.org/cgi/content/abstract/1632821100v1].
"We found that O-GlcNAc residues on cellular proteins can be metabolically labeled with azido groups, which primes them for chemical modification via the Staudinger ligation, a reaction we developed a few years back for specific bioconjugation," Bertozzi explains. "Using this chemistry on whole cell lysates, we were able to discriminate proteins modified with O-GlcNAc from the rest of the proteome--setting the stage for an inventory of the complete repertoire of O-GlcNAc-modified proteins.
Related sites:
Carolyn Bertozzi research group
