- Anomeric Selectivity of Trehalose Transferase with Rare l -Sugars
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Retaining LeLoir glycosyltransferases catalyze the formation of glycosidic bonds between nucleotide sugar donors and carbohydrate acceptors. The anomeric selectivity of trehalose transferase from Thermoproteus uzoniensis was investigated for both d- and l-glycopyranose acceptors. The enzyme couples a wide range of carbohydrates, yielding trehalose analogues with conversion and enantioselectivity of >98%. The anomeric selectivity inverts from α,α-(1 → 1)-glycosidic bonds for d-glycopyranose acceptors to α,β-(1 → 1)-glycosidic bonds for l-glycopyranose acceptors, while (S)-selectivity was retained for both types of sugar acceptors. Comparison of protein crystal structures of trehalose transferase in complex with α,α-trehalose and an unnatural α,β-trehalose analogue highlighted the mechanistic rationale for the observed inversion of anomeric selectivity.
- Bento, Isabel,Hagedoorn, Peter-Leon,Hanefeld, Ulf,Jeffries, Cy M.,Laustsen, Jesper U.,Marsden, Stefan R.,Mestrom, Luuk,Svergun, Dmitri I.,Van Der Eijk, Hessel
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p. 8835 - 8839
(2020/09/18)
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- Synthesis of 1,5-Anhydro-D-fructose derivatives and evaluation of their inflammasome inhibitors
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Synthesis of several 1,5-Anhydro-D-fructose (1,5-AF) derivatives to evaluate inhibitory activities of the inflammasome was carried out. Recently, 1,5-AF reported to suppress the inflammasome, although with only low activity. We focused on the hydration of
- Goto, Kohtaro,Ideo, Hiroko,Tsuchida, Akiko,Hirose, Yuriko,Maruyama, Ikuro,Noma, Satoshi,Shirai, Takashi,Amano, Junko,Mizuno, Mamoru,Matsuda, Akio
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supporting information
p. 3763 - 3772
(2018/07/13)
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- KinITC—One Method Supports both Thermodynamic and Kinetic SARs as Exemplified on FimH Antagonists
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Affinity data, such as dissociation constants (KD) or inhibitory concentrations (IC50), are widely used in drug discovery. However, these parameters describe an equilibrium state, which is often not established in vivo due to pharmacokinetic effects and they are therefore not necessarily sufficient for evaluating drug efficacy. More accurate indicators for pharmacological activity are the kinetics of binding processes, as they shed light on the rate of formation of protein–ligand complexes and their half-life. Nonetheless, although highly desirable for medicinal chemistry programs, studies on structure–kinetic relationships (SKR) are still rare. With the recently introduced analytical tool kinITC this situation may change, since not only thermodynamic but also kinetic information of the binding process can be deduced from isothermal titration calorimetry (ITC) experiments. Using kinITC, ITC data of 29 mannosides binding to the bacterial adhesin FimH were re-analyzed to make their binding kinetics accessible. To validate these kinetic data, surface plasmon resonance (SPR) experiments were conducted. The kinetic analysis by kinITC revealed that the nanomolar affinities of the FimH antagonists arise from both (i) an optimized interaction between protein and ligand in the bound state (reduced off-rate constant koff) and (ii) a stabilization of the transition state or a destabilization of the unbound state (increased on-rate constant kon). Based on congeneric ligand modifications and structural input from co-crystal structures, a strong relationship between the formed hydrogen-bond network and koff could be concluded, whereas electrostatic interactions and conformational restrictions upon binding were found to have mainly an impact on kon.
- Zihlmann, Pascal,Silbermann, Marleen,Sharpe, Timothy,Jiang, Xiaohua,Mühlethaler, Tobias,Jakob, Roman P.,Rabbani, Said,Sager, Christoph P.,Frei, Priska,Pang, Lijuan,Maier, Timm,Ernst, Beat
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supporting information
p. 13049 - 13057
(2018/08/17)
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- Synthesis, improved antisense activity and structural rationale for the divergent RNA affinities of 3′-fluoro hexitol nucleic acid (FHNA and Ara-FHNA) modified oligonucleotides
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The synthesis, biophysical, structural, and biological properties of both isomers of 3′-fluoro hexitol nucleic acid (FHNA and Ara-FHNA) modified oligonucleotides are reported. Synthesis of the FHNA and Ara-FHNA thymine phosphoramidites was efficiently acc
- Egli, Martin,Pallan, Pradeep S.,Allerson, Charles R.,Prakash, Thazha P.,Berdeja, Andres,Yu, Jinghua,Lee, Sam,Watt, Andrew,Gaus, Hans,Bhat, Balkrishen,Swayze, Eric E.,Seth, Punit P.
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supporting information; experimental part
p. 16642 - 16649
(2011/12/13)
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- First total synthesis of a fluorinated calystegin
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A straightforward chiral pool synthesis for the first fluorinated calystegin is described. Key steps of this synthesis include an ultrasound-assisted Zn-mediated tandem ring opening reaction followed by a Grubbs' catalyst-mediated ring closure metathesis
- Csuk, Rene,Prell, Erik,Reissmann, Stefan,Korb, Claudia
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experimental part
p. 445 - 451
(2010/10/01)
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- THE SYNTHESIS AND HYDROLYSIS OF A SERIES OF DEOXYFLUORO-D-GLUCOPYRANOSYL PHOSPHATES
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The synthesis of all four deoxyfluoro-α-D-glucopyranosyl phosphates is described.Rate conctants for their acid-catalyzed hydrolysis were determined, and fluorine substitution was shown to have a significant effect in lowering the rate, particularly when t
- Withers, Stephen G.,MacLennan, David J.,Street, Ian P.
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p. 127 - 144
(2007/10/02)
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- Chemoenzymatic Syntheses of Fluoro Sugar Phosphates and Analogues
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Combined chemical and enzymatic procedures are described for the preparation of fluorinated sugar phosphates and analogues.These derivatives are useful for study of sugar metabolism and for synthesis of pharmacological probes in a number of enzymatic systems utilizing sugars.
- Drueckhammer, Dale G.,Wong, Chi-Huey
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p. 5912 - 5913
(2007/10/02)
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- PREPARATION OF 3-DEOXY-3-FLUORO-D-MANNOSE AND CORRESPONDING HEXITOL
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Reaction of 1,6:3,4-dianhydro-β-D-altropyranose (I) with potassium hydrogen fluoride in hot ethylene glycol gave 1,6-anhydro-3-deoxy-3-fluoro-β-D-mannopyranose (II).On acid catalysed hydrolysis or acetolysis of compound II 3-deoxy-3-fluoro-D-mannose (VIII) or its tetra-O-acetyl derivative VII, respectively, were obtained.Reduction of compound VIII with sodium borohydride gave 3-deoxy-3-fluoro-D-mannitol (IX).The structures of the mentioned compounds were proved by 1H NMR spectroscopy.
- Cerny, Miloslav,Dolezalova, Jitka,Macova, Jindra,Pacak, Josef,Trnka, Tomas,Budesinsky, Milos
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p. 2693 - 2700
(2007/10/02)
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