Expanding the diversity of unnatural cell surface sialic acids

Journal Article · Thu Oct 30 04:00:00 EST 2003 · ChemBioChem

OSTI ID:839230

Luchansky, Sarah J ^[1]; Goon, Scarlett; Bertozzi, Carolyn R

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1. LBNL Library

Novel chemical reactivity can be introduced onto cell surfaces through metabolic oligosaccharide engineering. This technique exploits the substrate promiscuity of cellular biosynthetic enzymes to deliver unnatural monosaccharides bearing bioorthogonal functional groups into cellular glycans. For example, derivatives of N-acetylmannosamine (ManNAc) are converted by the cellular biosynthetic machinery into the corresponding sialic acids and subsequently delivered to the cell surface in the form of sialoglycoconjugates. Analogs of N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc) are also metabolized and incorporated into cell surface glycans, likely through the sialic acid and GalNAc salvage pathways, respectively. Furthermore, GlcNAc analogs can be incorporated into nucleocytoplasmic proteins in place of {beta}-O-GlcNAc residues. These pathways have been exploited to integrate unique electrophiles such as ketones and azides into the target glycoconjugate class. These functional groups can be further elaborated in a chemoselective fashion by condensation with hydrazides and by Staudinger ligation, respectively, thereby introducing detectable probes onto the cell. In conclusion, sialic acid derivatives are efficient vehicles for delivery of bulky functional groups to cell surfaces and masking of their hydroxyl groups improves their cellular uptake and utilization. Furthermore, the successful introduction of photoactivatable aryl azides into cell surface glycans opens up new avenues for studying sialic acid-binding proteins and elucidating the role of sialic acid in essential processes such as signaling and cell adhesion.

• Research Organization: Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA (US)
• Sponsoring Organization: USDOE Director. Office of Science. Office of Basic Energy Sciences. Division of Materials Sciences; National Institutes of Health GM58867 (US)
• DOE Contract Number: AC03-76SF00098
• OSTI ID: 839230
• Report Number(s): LBNL--54418
• Journal Information: ChemBioChem, Journal Name: ChemBioChem Journal Issue: 3 Vol. 5
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ADHESION
AZIDES
ENZYMES
FUNCTIONALS
HYDRAZIDES
KETONES
MACHINERY
MONOSACCHARIDES
OLIGOSACCHARIDES
PROBES
PROTEINS
RESIDUES
SIALIC ACID
SUBSTRATES
TARGETS