School of Chemistry - Research Publications
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ItemDifferentiation of aminohydroxypropanesulfonic acid structural isomers using tandem mass spectrometry-based methods(Elsevier BV, 2023-09)D-Cysteinolic acid (D-CA) is an important metabolite within the biosulfur cycle. A structural isomer, (R)-3-amino-2-hydroxypropanesulfonate ((R)-AHPS), is less common in nature but potentially can be misidentified as D-CA due to their many shared physical properties. To support confident assignment of these two isomers by use of mass spectrometry alone, this study explores the fragmentation reactions of their [M + H]+ and [M - H]- ions using collision-induced dissociation (CID). Electrospray ionization mass spectrometry (ESI-MS) experiments were conducted on authentic standards using an ion trap mass spectrometer, while a triple-quadrupole (QqQ) mass spectrometer was used in the selective reaction monitoring (SRM) mode to record energy-resolved CID. Density-functional theory (DFT) calculations were carried out at the M06/6-31+G* level of theory to study gas-phase fragmentation mechanisms. The data generated revealed kinetically-controlled fragmentations involving participation of neighboring amino groups in the positive ion mode. Negative ion mode MS analysis could distinguish the structural isomers through different collision energy-resolved results for m/z 95 product ions, CH3SO3−. DFT calculations revealed an enthalpy (ΔH) (Gibbs energy (ΔG)) gap of 31.8 (31.4) kJ/mol between transition state barriers of a concerted mechanism for D-CA, and a more preferred stepwise mechanism for (R)-AHPS.
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ItemNo Preview AvailableChemistry and biology of the aminosulfonate cysteinolic acid: discovery, distribution, synthesis and metabolism(ROYAL SOC CHEMISTRY, 2022-04-13)D-Cysteinolic acid is a zwitterionic aminosulfonate found in marine (and occasionally freshwater) environments. It is distributed in a wide range of algae (red, green and brown algae and diatoms), and some bacteria and sea animals. It was discovered in 1957 and in spite of its long history, its biosynthesis and degradation is poorly understood. Cysteinolic acid is found conjugated to steroids, lipids and arsenosugars, and the cysteinolic acid motif is found within the structures of various capnoid and sulfoceramide sulfonolipids. This review provides an historical account of the discovery of D-cysteinolic acid and related molecules, its distribution and occurrence within marine and freshwater organisms, routes for its chemical synthesis, and summarizes knowledge and speculations surrounding its biosynthesis, degradation and bioconversions.
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ItemNo Preview AvailableSynthesis of the Alkylsulfonate Metabolites Cysteinolic Acid, 3-Amino-2-hydroxypropanesulfonate, and 2,3-Dihydroxypropanesulfonate(AMER CHEMICAL SOC, 2022-03-18)Chiral hydroxy- and aminohydroxysulfonic acids are widespread in the marine and terrestrial environment. Here we report simple methods for the synthesis of d- and l-cysteinolic acid (from (Boc-d-Cys-OH)2 and (Boc-l-Cys-OH)2, respectively), R- and S-3-amino-2-hydroxypropanesulfonate (from S- and R-epichlorohydrin, respectively), and R- and S-2,3-dihydroxypropanesulfonate (from S- and R-epichlorohydrin, respectively). d-Cysteinolate bile salts were generated by coupling with cholic and chenodeoxycholic acids. A series of single-crystal 3D X-ray structures confirmed the absolute configurations of the aminosulfonates. By comparison of optical rotation, we assign naturally occurring 3-amino-2-hydroxypropanesulfonate from Gateloupia livida as possessing the R-configuration. This simple synthetic approach will support future studies of the occurrence, chemotaxonomic distribution, and metabolism of these alkylsulfonates.
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ItemStructure, Function and Mechanism of N-Glycan Processing Enzymes: endo-alpha-1,2-Mannanase and endo-alpha-1,2-Mannosidase(Wiley, 2023-02)While most glycosidases that act on N-linked glycans remove a single sugar residue at a time, endo-α-1,2-mannosidases and endo-α-1,2-mannanases of glycoside hydrolase family GH99 cut within a chain and remove two or more sugar residues. They are stereochemically retaining enzymes that use an enzymatic mechanism involving an epoxide intermediate. Human endo-α-1,2-mannosidase (MANEA) trims glucosylated mannose residues; the endomannosidase pathway provides a glucosidase-independent pathway for glycoprotein maturation. Cell-active MANEA inhibitors alter N-glycan processing and reduce infectivity of dengue virus, demonstrating that MANEA has potential as a host-directed antiviral target. Sequence-related enzymes from gut Bacteroides spp. exhibit endo-α-1,2-mannosidase activity and are a fruitful test bed for structure-guided inhibitor development. The genes encoding the Bacteroides spp. enzymes sit within polysaccharide utilization loci and are preferential endo-α-1,2-mannanases.