Cell surface oligosaccharides play essential roles in the cell-cell recognition events associated with bacterial and viral infection, tumor cell metastasis and leukocyte adhesion at sites of inflammation. These important biological functions obviate importance of studying the enzymes that modulate oligosaccharide structures. We have developed a multidisciplinary program aimed at the study of two oligosaccharide-processing enzymes: carbohydrate sulfotransferases and proximal glycanases. The sulfotransferases have been implicated in the regulation of leukocyte adhesion to endothelium at sites of inflammation, but have not yet been identified at the molecular level. The proximal glycanases liberate N-linked oligosaccharides fromglycoproteins, yet their biological functions remain undefined. Our goals are to identify the mechanisms and biological functions of these enzymes using organic chemistry as a tool. We are synthesizing inhibitors of both classes of enzymes, which will be used to observe the effects of enzyme inhibition on the cellular expression of glycoconjugates. In the case of the sulfotransferases, the inhibitors we synthesize may have anti-inflammatory activity and serve as leads for a new generation of anti-inflammatory drugs. Our synthetic targets comprise complex glycoconjugates related to cell-associated glycoproteins. These molecules are among the most difficult to synthesize and characterize. Mass spectrometry willbe an essential tool for the characterization of our synthetic compounds due to their high molecular weight, their structural complexity and their chemical liability. The UCSF Mass Spectrometry Facility is the only facility in the area with state-of-the-art instrumentation and a staff with expertise in glycoconjugate characterization, both of which will be necessary to these projects.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001614-19
Application #
6308880
Study Section
Project Start
2000-03-01
Project End
2002-02-28
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
19
Fiscal Year
2000
Total Cost
$9,880
Indirect Cost
Name
University of California San Francisco
Department
Type
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
MacRae, Andrew J; Mayerle, Megan; Hrabeta-Robinson, Eva et al. (2018) Prp8 positioning of U5 snRNA is linked to 5' splice site recognition. RNA 24:769-777
Katsuno, Yoko; Qin, Jian; Oses-Prieto, Juan et al. (2018) Arginine methylation of SMAD7 by PRMT1 in TGF-?-induced epithelial-mesenchymal transition and epithelial stem-cell generation. J Biol Chem 293:13059-13072
Sahoo, Pabitra K; Smith, Deanna S; Perrone-Bizzozero, Nora et al. (2018) Axonal mRNA transport and translation at a glance. J Cell Sci 131:
Tran, Vy M; Wade, Anna; McKinney, Andrew et al. (2017) Heparan Sulfate Glycosaminoglycans in Glioblastoma Promote Tumor Invasion. Mol Cancer Res 15:1623-1633
Liu, Tzu-Yu; Huang, Hector H; Wheeler, Diamond et al. (2017) Time-Resolved Proteomics Extends Ribosome Profiling-Based Measurements of Protein Synthesis Dynamics. Cell Syst 4:636-644.e9
Bikle, Daniel D (2016) Extraskeletal actions of vitamin D. Ann N Y Acad Sci 1376:29-52
Twiss, Jeffery L; Fainzilber, Mike (2016) Neuroproteomics: How Many Angels can be Identified in an Extract from the Head of a Pin? Mol Cell Proteomics 15:341-3
Cil, Onur; Phuan, Puay-Wah; Lee, Sujin et al. (2016) CFTR activator increases intestinal fluid secretion and normalizes stool output in a mouse model of constipation. Cell Mol Gastroenterol Hepatol 2:317-327
Posch, Christian; Sanlorenzo, Martina; Vujic, Igor et al. (2016) Phosphoproteomic Analyses of NRAS(G12) and NRAS(Q61) Mutant Melanocytes Reveal Increased CK2? Kinase Levels in NRAS(Q61) Mutant Cells. J Invest Dermatol 136:2041-2048
Julien, Olivier; Zhuang, Min; Wiita, Arun P et al. (2016) Quantitative MS-based enzymology of caspases reveals distinct protein substrate specificities, hierarchies, and cellular roles. Proc Natl Acad Sci U S A 113:E2001-10

Showing the most recent 10 out of 630 publications