Gary C. Look

Enzyme-catalyzed oligosaccharide synthesis☆

Cell-surface carbohydrates and their conjugates are involved in many types of molecular recognition. This review describes recent developments in enzyme-catalyzed oligosaccharide synthesis, with particular focus on glycosyltransferase and glycosidase reactions. With the increasing availability of glycosyltransferases via recombinant DNA technology, glycosyltransferase-catalyzed glycosylation with in situ regeneration of sugar nucleotides appears to be the most effective method for large-scale stereocontrolled oligosaccharide synthesis.

Trimethylorthoformate: A mild and effective dehydrating reagent for solution and solid phase imine formation

Abstract Trimethylorthoformate has been found to be an effective dehydrating solvent for the formation of imines, both in the solid phase as well as solution phase.

THE IDENTIFICATION OF CYCLOOXYGENASE-1 INHIBITORS FROM 4-THIAZOLIDINONE COMBINATORIAL LIBRARIES

Abstract Three 4-thiazolidinone libraries, each containing up to 540 compounds, were prepared and assayed for inhibition of the enzyme cyclooxygenase-1 (COX-1). Deconvolution analysis led to the identification of a compound that is equipotent with the commercial COX-1 inhibitors ibuprofen and phenylbutazone.

Synthesis of novel disaccharides based on glycosyltransferases: β1,4galactosyltransferase☆

Abstract β1,4Galactosyltransferase and β-galactosidase have been investigated with regard to their acceptor specificity and used in the synthesis of galactosides using 5-thioglucose, deoxyazaglucose, glucal, modified N-acetylglucosamine and glucose derivatives as acceptors.

A facile enzymatic synthesis of galβ1,3glucal: a key intermediate for the synthesis of Lea and sialyl Lea

Abstract Several glycosidases have been investigated with respect to their regioselectivity in the formation of glyclosidic bonds between various donor sugars and glycal acceptors. Of key interest is the β-galactosidase-mediated coupling of galactose to glucal affording the β-1,3-linked disaccharide with high regioselectivity.

Practical synthesis of carbohydrates based on aldolases and glycosyl transferases

With various recombinant DNA and protein engineering techniques now available, enzyme-bad technologies are emerging as practical methods for large-scale synthesis of chiral intermediates and bioactive molecules, especially carbohydrates, oligosaccharides, their conjugates and related substances. This paper describes recent developments in the synthesis of novel monosaccharides and aza sugars based on aldolases, and the synthesis of oligosaccharides and analogs based on glycosyltransferases coupled with in sins regeneration of sugar nucleotides. As many enzymes are available for the stereocontrolled synthesis of chiral synthons (l), attention has been extended to the development of more effective and stable enzymes for the synthesis of molecules with increasing complexity (2). One class of such complex molecules are carbohydrates and their conjugates, especially those that exist on cell surfaces (3). These molecules are involved in many types of recognition phenomena (3-6); however, most of their precise functions have not been clearly identified at the molecular level. Part of the reason is that these molecules have been difficult to isolate, characterize and synthesize. Enzyme-based technology seems to be well suited for the synthesis of glycoconjugates and related substances for the study of their functions as these molecules are multifunctional and highly soluble in polar solvents, and many enzymes are available for the transformation of these molecules (7). The following describes some new technologies developed for the synthesis of sugar- and peptide- related substances based on recombinant or engineered enzymes.

Chemical-Enzymatic Synthesis of Carbohydrates

This paper describes the use of three types of enzymes in carbohydrate synthesis. Aldolases are a useful class of catalysts for the synthesis of aza sugars and related compounds. Glycosyltransferases have been developed for the synthesis of oligosaccharides. The enzymatic oligosaccharide synthesis has been proven effective and practical when coupled with in situ regeneration of sugar nucleotides. A subtilisin variant prepared via site-directed mutagenesis is stable and active in dimethylformamide and is useful for regioselective acylation of sugars.