Synthesis of fluorinated analogues of lipid A

Vyplel, H.; Scholz, D.; Loibner, Hans; Kern, Michael; Bednarik, Karl; Schaller, H.

doi:10.1016/s0040-4039(00)91596-x

Cited by 11 publications

(3 citation statements)

References 13 publications

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“…Analogues of -glucose carrying a substitution OH F at positions 2, 3, 4 or 6, the αand β-anomers of -glucopyranosyl fluoride and 2-deoxy-2-fluoro-α--glucopyranosyl fluoride were synthesized by reported protocols [25]. 2-Deoxy-2-fluoro-Glc 1-P was synthesized by following a general procedure reported previously [26]. All compounds were characterized fully by melting points and analysis of "H-, "$Cand "*F-NMR spectra.…”

Section: Synthesis Of Substrate Analoguesmentioning

confidence: 99%

Role of non-covalent enzyme‒substrate interactions in the reaction catalysed by cellobiose phosphorylase from Cellulomonas uda

2000

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Steady-state kinetic studies of the enzymic glucosyl transfer to and from phosphate catalysed by cellobiose phosphorylase from Cellulomonas uda have shown that this enzyme operates by a ternary-complex kinetic mechanism in which beta-cellobiose binds before phosphate, and beta-D-glucose and alpha-D-glucopyranosyl phosphate are released in that order. alpha-D-Glucopyranosyl fluoride (but not beta-D-glucopyranosyl fluoride) serves as alternative glucosyl donor for beta-cellobiose synthesis with a specificity constant that is one-ninth that of the corresponding enzymic reaction with alpha-D-glucopyranosyl phosphate (approximately 20000 M(-1).s(-1) at 30 degrees C). The kinetic parameters for a complete series of deoxy and deoxyfluoro analogues of D-glucose have been determined and the data yield estimates of the net strengths of hydrogen-bonding interactions with the non-reacting hydroxy groups of D-glucose at the transition state (0.8-4.0 kcal/mol, where 1 cal identical with 4.184 J) and enable the prediction of the polarities of these hydrogen bonds. Each hydroxy group functions as donor of a hydrogen for bonding to probably a charged (at 3-OH) or neutral (at 2-OH and 6-OH) acceptor group on the enzyme. The equatorial 1-OH is essential for enzyme activity. Derivatives of D-glucose in which the 1-OH or the reacting 4-OH were replaced by hydrogen or fluorine have been tested as inhibitors to measure their affinities for the sugar-binding subsite +1 (numbered from the bond-cleaving/forming site). The data show that hydrogen-bonding interactions between the 1-OH and 4-OH and charged groups on the enzyme stabilize the ground-state ternary complex of the enzymic synthesis of beta-cellobiose by 2.3 and 0.4 kcal/mol, respectively, and assist the precise positioning of beta-D-glucose for catalysis.

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Section: Synthesis Of Substrate Analoguesmentioning

confidence: 99%

Role of non-covalent enzyme‒substrate interactions in the reaction catalysed by cellobiose phosphorylase from Cellulomonas uda

2000

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“…He prepared such sugars using AcOF and mixed them with certain lipid saccharides in the presence of lipid synthase demonstrating easy reversible transfer of the lipid chain to the fluorosugar. 76 Labeled acetyl hypofluorite was also used for fluorination of antipyrine and uracil. The corresponding radioactive fluoro derivatives resulted through an addition elimination mechanism (Scheme 45).…”

Section: Acetyl Hypofluorite and Higher Homologsmentioning

confidence: 99%

“…The great biological importance of fluorosugars, especially for antiviral treatments, is beyond the scope of this review, but we mention Vyplel's work on proving that many enzymatic processes will treat fluorosugars as practically natural substrates. He prepared such sugars using AcOF and mixed them with certain lipid saccharides in the presence of lipid synthase demonstrating easy reversible transfer of the lipid chain to the fluorosugar …”

Section: Acetyl Hypofluorite and Higher Homologsmentioning

confidence: 99%