Glycoside hydrolase stabilization of transition state charge: new directions for inhibitor design.

Carbasugars are structural mimics of naturally occurring carbohydrates that can interact with and inhibit enzymes involved in carbohydrate processing. In particular, carbasugars have attracted attention as inhibitors of glycoside hydrolases (GHs) and as therapeutic leads in several disease areas. However, it is unclear how the carbasugars are recognized and processed by GHs.

Author Correction: Revealing the mechanism for covalent inhibition of glycoside hydrolases by carbasugars at an atomic level.

In the originally published version of this Article, the affiliation details for Tracey M. Gloster were incorrectly given as 'Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada'. The correct affiliation is 'Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK'.

Revealing the mechanism for covalent inhibition of glycoside hydrolases by carbasugars at an atomic level.

Mechanism-based glycoside hydrolase inhibitors are carbohydrate analogs that mimic the natural substrate's structure. Their covalent bond formation with the glycoside hydrolase makes these compounds excellent tools for chemical biology and potential drug candidates. Here we report the synthesis of cyclohexene-based α-galactopyranoside mimics and the kinetic and structural characterization of their inhibitory activity toward an α-galactosidase from Thermotoga maritima (TmGalA).

Software for rapid time dependent ChIP-sequencing analysis (TDCA).

Background: Chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) and associated methods are widely used to define the genome wide distribution of chromatin associated proteins, post-translational epigenetic marks, and modifications found on DNA bases. An area of emerging interest is to study time dependent changes in the distribution of such proteins and marks by using serial ChIP-seq experiments performed in a time resolved manner. Despite such time resolved studies becoming increasingly common, software to facilitate analysis of such data in a robust automated manner is limited.

Observation of a Tricyclic[4.1.0.0]heptane During a Michael Addition-Ring Closure Reaction and a Computational Study on Its Mechanism of Formation.

We describe the formation of a bis-cyclopropane product, a tricyclic[4.1.0.

Crystal Structure and Properties of Imidazo-Pyridine Ionic Liquids.

Computational studies were performed on novel protic ionic liquids imidazolium-[1,2-a]-pyridine trifluoroacetate [ImPr][TFA] synthesized by the reaction of imidazo-[1,2a]-pyridine (ImPr) with trifluoroacetic acid (TFA), and on fused salt imidazolium-[1,2-a]-pyridine maleamic carbonate [ImPr][Mal] synthesized by reaction of ImPr with maleamic acid (Mal). Synthesis was performed as one-pot reactions, which applies green chemistry tenets. Both these compounds begin to decompose at 180°C.

C2-Oxyanion Neighboring Group Participation: Transition State Structure for the Hydroxide-Promoted Hydrolysis of 4-Nitrophenyl α-d-Mannopyranoside.

The hydroxide-catalyzed hydrolysis of aryl 1,2-trans-glycosides proceeds through a mechanism involving neighboring group participation by a C2-oxyanion and rate-limiting formation of a 1,2-anhydro sugar (oxirane) intermediate. The transition state for the hydroxide-catalyzed hydrolysis of 4-nitrophenyl α-d-mannopyranoside in aqueous media has been studied by the use of multiple kinetic isotope effect (KIE) measurements in conjunction with ab initio theoretical methods. The experimental KIEs are C1-H (1.