Conformationally locked thiosugars as potent α-mannosidase inhibitors: Synthesis, biochemical and docking studies

Sivapriya, K.; Hariharaputran, Sridhar; Suhas, V. L.; Chandra, Nagasuma; Chandrasekaran, Srinivasan

doi:10.1016/j.bmc.2007.06.011

Cited by 18 publications

(11 citation statements)

References 10 publications

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“…In this conformation, the sulfonyl oxygens may be in position to act as H-bond acceptors from the general acid aspartate and/or other donor residues in the active site. Support for this idea is found in the studies of Sivapriya et al 4 , who showed that a sulfone inhibitor of αmannosidase binds much better than the corresponding sulfide. Furthermore, calculational docking studies suggest that the sulfonyl oxygens form important H-bonds with carboxylates and other donors in the active site.…”

Section: Effects Of Covalent Modification Of Long Oga On Its O-glcnacase Activity and Its Cleavage By Caspasementioning

confidence: 89%

“…Bottom: Sulfone inhibitor of α-mannosidase described by Sivapriya et al, along with H-bonding interactions in the active site predicted by docking studies. 4 The corresponding sulfide binds much more poorly, implicating the sulfone oxygens as important H-bond acceptors.…”

Section: Effects Of Covalent Modification Of Long Oga On Its O-glcnacase Activity and Its Cleavage By Caspasementioning

confidence: 99%

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Distinctive Inhibition of O-GlcNAcase Isoforms by an α-GlcNAc Thiolsulfonate

et al. 2007

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O-GlcNAcase (OGA) promotes O-GlcNAc removal, and thereby plays a key role in O-GlcNAc metabolism, a feature of a variety of vital cellular processes. Two splice transcripts of human OGA encode "long OGA", which contains a distinct N-terminal O-GlcNAcase domain and a C-terminal histoneacetylferase (HAT) domain, and "short OGA", which lacks the HAT domain. The functional roles of long OGA are only beginning to be unraveled, and the characteristics of short OGA remain almost unknown. We find that short OGA, which possesses O-GlcNAcase catalysis machinery like that of long OGA, exhibits comparative resistance to previously described potent inhibitors of long OGA and lysosomal hexosaminidases, including PUGNAc and NAG-thiazoline, suggesting a role for the HAT domain in O-GlcNAcase catalysis. We also find that alpha-GlcNAc thiolsulfonate (2) is the most potent inhibitor of short OGA yet described (Ki = 10 microM), and exhibits some degree of selectivity versus long OGA and lysosomal hexosaminidases. In contrast to its mode of inhibition of short OGA, 2 acts as a irreversible inhibitor of long OGA by covalently modifying the enzyme as an S-GlcNAc derivative. Covalent attachment of GlcNAc to the HAT domain of long OGA dramatically changes its properties with respect to enzymatic activity and caspase-3 cleavage.

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Section: Effects Of Covalent Modification Of Long Oga On Its O-glcnacase Activity and Its Cleavage By Caspasementioning

confidence: 89%

Section: Effects Of Covalent Modification Of Long Oga On Its O-glcnacase Activity and Its Cleavage By Caspasementioning

confidence: 99%

Distinctive Inhibition of O-GlcNAcase Isoforms by an α-GlcNAc Thiolsulfonate

et al. 2007

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“…MD2 phytase with IP 6 , in an attempt to understand the lack of activity of the enzyme in the presence of Zn 2+ . AutoDock has earlier been used to dock ligands to metallo-proteins [20][21][22]. The Yasara software ranked the conformations generated in the docking runs based on the binding energy, the first rank representing the more likely or energetically favored conformation.…”

Section: Probing the Binding Of Ip 6 To Ca-and Zn-phytasementioning

confidence: 99%

Thermostable alkaline phytase from Bacillus sp. MD2: Effect of divalent metals on activity and stability

Tran

Hashim

Gaber

et al. 2011

Journal of Inorganic Biochemistry

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“…It has been possible to synthesize ferrocene‐tagged chiral amine derivatives 10a and 10b by ring opening of optically pure aziridine 10 derived from phenylalanine. The initially formed N ‐tosylsulfonamido disulfide9e and thiolate derived from the cleavage of this disulfide was trapped with 4 and 5 to furnish 10a and 10b . In the case of chloroacetamides 9 and 11 the reaction proceeded faster than for 8 and 10 indicating that they were more reactive substrates towards tetrathiomolybdate ( 1 ).…”

Section: Resultsmentioning

confidence: 99%

Convenient Synthesis of Ferrocene Conjugates Mediated by Benzyltriethylammonium Tetrathiomolybdate in a Multi‐Step Tandem Process

2009

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The synthesis of a wide range of ferrocene‐derived sulfur‐linked mono‐ and disubstituted Michael adducts and conjugates mediated by benzyltriethylammonium tetrathiomolybdate (1) in a tandem process is reported. New route to access acryloylferrocene (4) and 1,1′‐diacryloylferrocene (5) is discussed. Conjugation of amino acids to ferrocene is established via their N and C termini and also via side chains employing conjugate addition as key step to furnish mono‐ and divalent conjugates. This methodology has also been extended to access several ferrocene–carbohydrate conjugates. The electrochemical behavior of some selected ferrocene conjugates was studied by cyclic voltammetry. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

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Conformationally locked thiosugars as potent α-mannosidase inhibitors: Synthesis, biochemical and docking studies

Cited by 18 publications

References 10 publications

Distinctive Inhibition of O-GlcNAcase Isoforms by an α-GlcNAc Thiolsulfonate

Distinctive Inhibition of O-GlcNAcase Isoforms by an α-GlcNAc Thiolsulfonate

Thermostable alkaline phytase from Bacillus sp. MD2: Effect of divalent metals on activity and stability

Convenient Synthesis of Ferrocene Conjugates Mediated by Benzyltriethylammonium Tetrathiomolybdate in a Multi‐Step Tandem Process

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