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Novel UDP-glycal derivatives as transition state analogue inhibitors of UDP-GlcNAc 2-epimerase. 2004

Florian Stolz, and Martin Reiner, and Astrid Blume, and Werner Reutter, and Richard R Schmidt
Fachbereich Chemie, Universität Konstanz, Fach M725, D-78457 Konstanz, Germany.

The "epimerisation" of UDP-GlcNAc to ManNAc, the first step in the biosynthesis of sialic acids, is catalyzed by UDP-GlcNAc 2-epimerase. In this paper we report the synthesis of transition state based inhibitors of this enzyme. To mimic the assumed first transition state of this reaction (TS 1), we designed and synthesized the novel UDP-exo-glycal derivatives 1-4. We also report herein the synthesis of 5 and 6, the first C-glycosidic derivatives of 2-acetamidoglucal, and the synthesis of the ketosides 7 and 8, which were designed as bis-substrate analogue and bis- product analogue, respectively, to mimic the second step of the reaction via the assumed second transition state TS 2.

UI MeSH Term Description Entries
D002238 Carbohydrate Epimerases Enzymes that catalyze the epimerization of chiral centers within carbohydrates or their derivatives. EC 5.1.3. Carbohydrate Isomerases,Epimerases, Carbohydrate,Isomerases, Carbohydrate
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006595 Hexosamines AMINO SUGARS created by adding an amine group to a hexose sugar. Hexosamine
D012794 Sialic Acids A group of naturally occurring N-and O-acyl derivatives of the deoxyamino sugar neuraminic acid. They are ubiquitously distributed in many tissues. N-Acetylneuraminic Acids,Acids, N-Acetylneuraminic,Acids, Sialic,N Acetylneuraminic Acids
D013237 Stereoisomerism The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
D014530 Uridine Diphosphate A uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety. UDP,Uridine Pyrophosphate,Diphosphate, Uridine,Pyrophosphate, Uridine
D018716 Molecular Mimicry The structure of one molecule that imitates or simulates the structure of a different molecule. Antigenic Mimicry,DNA Mimicry,Mimicry, Molecular,Antigen Mimicry,Antigen Mimicries,Antigenic Mimicries,DNA Mimicries,Mimicries, Antigen,Mimicries, Antigenic,Mimicries, DNA,Mimicries, Molecular,Mimicry, Antigen,Mimicry, Antigenic,Mimicry, DNA,Molecular Mimicries

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