A Free-Energy Relationship between the Rate of Acidic Hydrolysis of Glycosides and the pKa of Isofagomines

Jensen, Hans Jørgen; Lyngbye, Laila; Bols, Mikael

doi:10.1002/1521-3773(20010917)40:18<3447::aid-anie3447>3.0.co;2-8

Cited by 75 publications

(47 citation statements)

References 23 publications

(10 reference statements)

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“…By comparing the p K a values for the conjugate acid it was found that equatorial substituents are significantly more deactivating (EWD) than their axial counterparts. 25,26,27,28 The same effects were found for glycosyl donors and used by Bols and co-workers to conformationally arm glycosyl donors by changing the equatorial rich 4 C 1 conformation to an axial rich conformation. 29,30,31,32,33 The conformational changes were induced by creating steric congestion at the equatorial C-2, C-3 and C-4 positions of D-glucosides, 34 resulting in a skew-boat conformation (donor B1 , Scheme 1B).…”

supporting

confidence: 60%

Superarming of Glycosyl Donors by Combined Neighboring and Conformational Effects

et al. 2013

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supporting

confidence: 60%

Superarming of Glycosyl Donors by Combined Neighboring and Conformational Effects

et al. 2013

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“…Judging from the K d value of 3 (0.76 M), the compound appears to have the highest affinity among the lysozyme inhibitors identified to date. The pH dependence of ⌬G r°f or 3 (Table 4) might be derived from the change in the protonation state of the moranoline moiety, of which the pK a value was reported to be 6.3-6.7 (13,31). The protonation state of Glu-35 (pK a ϭ 6.7, Ref.…”

Section: Discussionmentioning

confidence: 99%

A Novel Transition-state Analogue for Lysozyme, 4-O-β-Tri-N-acetylchitotriosyl Moranoline, Provided Evidence Supporting the Covalent Glycosyl-enzyme Intermediate*

Ogata

Umemoto

Ohnuma

et al. 2013

Journal of Biological Chemistry

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Backgroud: A pure and stable transition-state analogue for lysozyme has not been reported thus far. Results: We synthesized 4-O-␤-tri-N-acetyl-chitotriosyl moranoline (3), which inhibited strongly the lysozyme reaction. Conclusion: Compound 3 was found to be a novel and stable transition-state analogue for lysozyme. Significance: The crystal structure of lysozyme in a complex with 3 supports the covalent glycosyl-enzyme intermediate in the catalytic reaction. Lysozymes (EC 3.2.1.17) are glycosidases acting in the innate-immune system of most animals (1). The common feature of lysozymes is to exert antibacterial activity by cleaving the ␤-1,4-glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine (GlcNAc) 5 in peptidoglycan, a major bacterial cell-wall component (2). Hen egg white lysozyme (HEWL) was the first enzyme to have its three-dimensional structure determined by x-ray crystallography, revealing that the enzyme is divided into two domains by a deep substratebinding cleft containing the catalytic site (3). The catalytic importance of the conserved residues, Glu-35 and Asp-52, was also confirmed by the crystal structure of the enzyme-ligand complex (4) and site-directed mutagenesis (5). These studies on the structure and function of HEWL offer the strongest support available to date for the theory that enzymes may catalyze reactions by binding substrates in the geometry of the transition state more strongly than in that of the ground state. 4-O-␤-HEWL has six subsites for sugar residue binding, termed Ϫ4 to ϩ2 (formerly A, B, C, D, E, and F (6)). The enzyme cleave a glycosidic linkage between the sugar residues at subsites Ϫ1 and ϩ1 with the aid of the proton-donating action of Glu-35 as a general acid. The substrate analog tri-N-acetylchitotriose, (GlcNAc) 3 , binds predominantly to subsites Ϫ4, Ϫ3, and Ϫ2 of HEWL, keeping away from subsite Ϫ1 due to the unfavorable positive free energy of the sugar residue binding at that subsite (7). This situation might have been an obstacle to understanding the catalytic mechanism of the enzyme. In the classical explanation, the lysozyme-catalyzed reaction was recognized to take place via a carbenium ion

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“…33 In contrast, a correlation has been observed between the reactivity and electronegativity of ring substituents. 24 In the case of furanosides the sugar ring configuration correlates more clearly with the reactivity. The substituents of adjacent carbon atoms in cis orientation can be expected to repel each other, and this repulsion is relieved as the sugar ring is opened and an acyclic oxocarbenium ion is formed.…”

Section: Discussionmentioning

confidence: 99%

Hydrolytic decomposition of glycosides in aqueous acids

Mikkola¹,

Oivanen²

2008

Arkivoc

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A review is presented that collects the experimental results published on the acid catalyzed hydrolysis of alkyl and aryl pyranosides and furanosides over the last three decades. In aqueous acid, alkyl furanosides and pyranosides are hydrolysed via an oxocarbenium intermediate, which may be formed from the protonated substrate either by an exocyclic or endocyclic C-O bond cleavage. Both mechanisms lead eventually to the same products. Various methods have been used to distinguish between the pathways, and a lot of evidence exists to show that different pathways are followed depending on the structure of both the glycon moiety and the departing alcohol.

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A Free-Energy Relationship between the Rate of Acidic Hydrolysis of Glycosides and the pKa of Isofagomines

Cited by 75 publications

References 23 publications

Superarming of Glycosyl Donors by Combined Neighboring and Conformational Effects

Superarming of Glycosyl Donors by Combined Neighboring and Conformational Effects

A Novel Transition-state Analogue for Lysozyme, 4-O-β-Tri-N-acetylchitotriosyl Moranoline, Provided Evidence Supporting the Covalent Glycosyl-enzyme Intermediate*

Hydrolytic decomposition of glycosides in aqueous acids

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