Georges Guillerm

A new series of cyclic amino acids as inhibitors of S-adenosyl L-methionine synthetase

Optically active 3-amino-3-(tetrahydrofuranyl) carboxylic acid, 3-amino-3-(tetrahydrothienyl) carboxylic acid and their corresponding six membered ring analogues have been synthesised and examined as potential inhibitors of the enzyme S-adenosylmethionine (AdoMet) synthetase. The kinetic behaviour of these compounds was studied using recombinant rat liver AdoMet synthetase (alpha-isoform) fractionated from E. coli transformed with the plasmid pSSRL-T7N. All the compounds tested were competitive inhibitors of the enzyme with respect to L-methionine.

Synthesis of new (difluoromethylphosphono)azadisaccharides designed as bisubstrate analogue inhibitors for GlcNAc:β-1,4 glycosyltransferases

We report here the design, synthesis and antifungal evaluation of a new model of bisubstrate analogue inhibitor for glycosyltransferases. The synthetic strategy relies on the reductive amination between the aldehyde derived from an N-allylphosphono-pyrrolidine and an aminosugar.

Synthesis of 6-deoxy-homoDMDP and its C(5)-epimer: absolute stereochemistry of natural products from Hyacinthus orientalis

Abstract A concise enantioselective synthesis of 2,5-imino-2,5,6-trideoxy- d -manno-heptitol (6-deoxy-homoDMDP) and 2,5-imino-2,5,6-trideoxy- l -gulo-heptitol has been achieved. These compounds were used as stereochemical references to establish the absolute configuration of the corresponding naturally occurring stereoisomers, recently isolated from Hyacinthus orientalis.

Enantioselective Synthesis of Epoxy Amino Acids

Abstract : New functionalized 4,5-Epoxy-α-aminoacids are prepared in two steps via iodolactonization of (S)-allylglycine and (S)-crotylglycines.

A NEW SERIES OF S-ADENOSYL- L-METHIONINE SYNTHETASE INHIBITORS

A new series of epithio and epoxy amino acid analogues of L-methionine or L-methoxinine were examined as potential inhibitors of the enzyme S-adenosylmethionine (AdoMet) synthetase. The kinetic behaviour of these compounds was studied using recombinant rat liver S-adenosyl-L-methionine sythetase (alpha-isoform) fractionated from E. coli, transformed with the plasmid pSSRL-T7N. All the compounds tested were competitive inhibitors with respect to L-methionine and the (2S, 4S)-2-amino-4,5-epoxy pentanoic acid was found to be a very potent inhibitor of the enzyme compared to those already reported for AdoMet synthetase from other mammalian tissues.

Inhibition of Chitin Synthetase from Saccharomyces cerevisiae by a New UDP-GlcNAc Analogue

The synthesis and biological evaluation of a new UDP-G1cNAc competitor (I), designed to mimic the transition state of the sugar donor in the enzymatic reaction catalysed by chitin synthetase, is described. Compound (I) was found to competitively inhibit chitin synthetase from Saccharomyces cerevisiae with respect to UDP-G1cNAc, but displayed minimal antifungal activity.

Kinetic properties of fluorinated substrate analogues on 5′-methylthioadenosine nucleosidase from Escherichia coli

Abstract 5′-Deoxy-5′-[(monofluoromethyl)thio]adenosine, 5′-deoxy-5′-[(difluoro-methyl)thio]adenosine and 5′-deoxy-5′-[(trifluoro-methyl)thio]adenosine have been evaluated for their substrate and inhibitory activities toward 5′-methylthioadenosine (MTA) nucleosidase from Escherichia coli . Their abilities to serve as substrates of MTA nucleosidase support the concept that MTA nucleosidase plays a role in the biological activity of these compounds.