Inhibition of glycosidases by substituted amidines
Five substituted amidines were examined as reversible inhibitors of glycosidases.
References (24)
- et al.
Glycobiology
(1992) - et al.
J. Am. Chem. Soc.
(1990) - et al.
Biochem. J.
(1989)et al.Bioorg. Med. Chem. Lett.
(1991)et al.Tetrahedron Lett.
(1993)et al.J. Am. Chem. Soc.
(1994) - et al.
Tetrahedron
(1989) - et al.
Adv. Enzymol. Relat. Areas Mol. Biol.
(1988) - et al.
Biochemistry
(1983)et al.Transition state affinity and the design of enzyme inhibitors
et al.J. Biol. Chem.
(1994) Chem. Rev.
(1990)Adv. Carbohydr. Chem. Biochem.
(1990)FASEB J.
(1991)- et al.
J. Am. Chem. Soc.
(1991)
J. Biol. Chem.
Am. Chem. Soc.
Cited by (28)
Targeting cancer via Golgi α-mannosidase II inhibition: How far have we come in developing effective inhibitors?
2021, Carbohydrate ResearchCitation Excerpt :Among all the derivatives explored, d-mannoamidrazone (8) and mannonhydroximolactam (9) are regarded as the most potent nanomolar inhibitors of JbMan, with no selectivity study found [60,107,108]. Other derivatives are mostly micromolar or millimolar inhibitors, which are inferior compared to swainsonine [105–107,109,110]. Unlike swainsonine, there is sustained research of d-mannose derivatives undertaken in the recent few years by several groups.
Using DFT methodology for more reliable predictive models: Design of inhibitors of Golgi α-Mannosidase II
2016, Journal of Molecular Graphics and ModellingCitation Excerpt :Zn2+ ion is in octahedral coordination with four amino acid residues (side chains of His90, Asp92, Asp204, His471) and an inhibitor (bidentate ligand). It is known from literature [6–20] that all potent GMII inhibitors have to bind properly to the bottom of the active site and interact with Zn2+ and neighboring amino acid residues, otherwise the potency of the inhibitor is dropped dramatically. Therefore, an accurate evaluation of interaction energy between the inhibitor and receptor sugar-binding catalytic site may be critical for a successful design of new potent and selective GMII inhibitors.
N-benzylgalactonoamidines as potent β-galactosidase inhibitors
2012, TetrahedronCitation Excerpt :However, only a few notable examples of the inhibitors in this compound class display inhibition of glycosidases in the nanomolar range.1 Efforts to improve the inhibitory ability of glyconoamidines of unsubstituted gluco- and benzylmannoamidines16–18 focused on the incorporation of supplementary electrostatic interaction to the glyconoamidine core by using aliphatic aglycons with and without additional N- or O-binding motifs,1 and the introduction of hydrophobic groups.19 Considerably less attention has been given to account for the lengthening of the glycosidic bond during the glycoside hydrolysis, which might play an important role for the interaction of an inhibitor with the active site in the enzyme.
Multi gram-scale synthesis of galactothionolactam and its transformation into a galactonoamidine
2011, Carbohydrate ResearchCitation Excerpt :To show proof of concept, we are in need of such compound in gram amounts, and therefore directed initial focus on synthesizing (3S,4S,5S,6R,Z)-2-(benzylimino)-6-(hydroxymethyl) piperidine-3,4,5-triol, N-benzylgalactonoamidine 1, as compound encompassing characteristics of the enzymatic galactoside hydrolysis (Scheme 1).3–6 Gluco- and mannoamidines have been reported previously as potent transition state analogs and competitive inhibitors of corresponding glycosidases.7–12 Comparable entities with the galacto-configuration are not described yet.
Glycosidase Inhibitors: Structure, Activity, Synthesis, and Medical Relevance
2007, Comprehensive Glycoscience: From Chemistry to Systems BiologyGlycosylamidines as potent selective and easily accessible glycosidase inhibitors and their application to affinity chromatography
2003, Methods in EnzymologyCitation Excerpt :Thus, the highly basic and permanently protonated amidinium ion is probably bound tightly by charge–charge interaction with the catalytic carboxy group(s) in the enzyme active site. In contrast to other strong glycosidase inhibitors, such as endocyclic glyconamidines17,18 and glycoimidazoles,39,40 β-glycosylamidines have an almost complete chair-shaped conformation with a sp3 anomeric carbon. This structural feature effectively recruits the specific interaction of the enzyme toward its substrates, thereby attaining selective inhibition according to the glycon and stereospecificities of the enzyme.
- b
Present address: Dyson Perrins Laboratory, South Parks Road, Oxford, OX1 3QY, U.K.