This research will develop enzymes as catalysts for the synthesis of carbohydrates and derivatives. It will: . Use aldolases and related enzymes -- particularly fructose-1,6- diphosphate aldolase, fuculose-1-phosphate aldolase, rhamnulose-1-phosphate aldolase and transketolase -- to make monosaccharides. . Synthesize the nucleoside phosphate sugars required for Leloir-pathway syntheses. . Continue to develop glycosyl transferases as catalysts for synthesis of oligosaccharides and polysaccharides via the Leloir pathway by practical procedures. . Use potato phosphorylase to prepare amylose conjugates of proteins and other molecules. . Develop strategies and techniques for using the products of enzyme- catalyzed syntheses of carbohydrates by preparing natural products and analogs of them: L-heptose, lincosamine, glycosidase inhibitors, neoglycoproteins, analogs of glycolipids. . Provide reagents and non-enzymatic reactions needed to support these efforts in enzyme-catalyzed synthesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM030367-12
Application #
3484681
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1982-04-01
Project End
1995-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
12
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Arts and Sciences
DUNS #
071723621
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Mack, Eric T; Snyder, Phillip W; Perez-Castillejos, Raquel et al. (2012) Dependence of avidity on linker length for a bivalent ligand-bivalent receptor model system. J Am Chem Soc 134:333-45
Mirica, Katherine A; Lockett, Matthew R; Snyder, Phillip W et al. (2012) Selective precipitation and purification of monovalent proteins using oligovalent ligands and ammonium sulfate. Bioconjug Chem 23:293-9
Mecinovic, Jasmin; Snyder, Phillip W; Mirica, Katherine A et al. (2011) Fluoroalkyl and alkyl chains have similar hydrophobicities in binding to the ""hydrophobic wall"" of carbonic anhydrase. J Am Chem Soc 133:14017-26
Snyder, Phillip W; Mecinovic, Jasmin; Moustakas, Demetri T et al. (2011) Mechanism of the hydrophobic effect in the biomolecular recognition of arylsulfonamides by carbonic anhydrase. Proc Natl Acad Sci U S A 108:17889-94
Mack, Eric T; Snyder, Phillip W; Perez-Castillejos, Raquel et al. (2011) Using covalent dimers of human carbonic anhydrase II to model bivalency in immunoglobulins. J Am Chem Soc 133:11701-15
Bilgi├žer, Ba?ar; Thomas 3rd, Samuel W; Shaw, Bryan F et al. (2009) A non-chromatographic method for the purification of a bivalently active monoclonal IgG antibody from biological fluids. J Am Chem Soc 131:9361-7
Krishnamurthy, Vijay M; Kaufman, George K; Urbach, Adam R et al. (2008) Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding. Chem Rev 108:946-1051
Mack, Eric T; Perez-Castillejos, Raquel; Suo, Zhigang et al. (2008) Exact analysis of ligand-induced dimerization of monomeric receptors. Anal Chem 80:5550-5
Semetey, Vincent; Moustakas, Demetri; Whitesides, George M (2006) Synthesis and conformational study of water-soluble, rigid, rodlike oligopiperidines. Angew Chem Int Ed Engl 45:588-91
Krishnamurthy, Vijay M; Quinton, Lee J; Estroff, Lara A et al. (2006) Promotion of opsonization by antibodies and phagocytosis of Gram-positive bacteria by a bifunctional polyacrylamide. Biomaterials 27:3663-74

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