Thioglycoligation of aromatic thiols using a natural glucuronide donor

Abstract

<p>β-D-glucuronidase DtGlcA from Dictyoglomus thermophilum was engineered to generate an active thioglycoligase able to catalyse the formation of numerous S-glucuronides. Its X-ray structure analysis indicated the ability of the biocatalyst...</p>

Biocatalytic Approaches to Building Blocks for Enzymatic and Chemical Glycan Synthesis

“… 137 , 138 Additionally, β- d -glucuronidase Dt GlcA from Dictyoglomus thermophilum has shown promise as a future thioglycoligase capable of catalyzing the formation of S -glucuronides. 139 Mutation of the catalytic E396 residue to glutamine led to an efficient catalyst for synthesizing a small panel of glucuronic acid thioglycosides and lays a foundation for the synthesis of S -glycoside building blocks. 140 …”

“…Glycosynthases obtained through mutagenesis of glycosyl hydrolases (removing/reducing hydrolysis activity) are an attractive alternative to glycosyltransferases as they do not require expensive ND­(M)­P-sugar donors. − The E338G mutant of the Thermus thermophilus glycoside hydrolase ( TT βGly E338G) was successfully used in combination with a glycosyl fluoride donor and C6-modified acceptor for the expeditious synthesis of lactose and lactosamine core thioglycosides (Figure B). , Additionally, β- d -glucuronidase Dt GlcA from Dictyoglomus thermophilum has shown promise as a future thioglycoligase capable of catalyzing the formation of S -glucuronides . Mutation of the catalytic E396 residue to glutamine led to an efficient catalyst for synthesizing a small panel of glucuronic acid thioglycosides and lays a foundation for the synthesis of S -glycoside building blocks …”

Insight on Mercapto-Coumarins: Synthesis and Reactivity

“…Enzymatic synthesis of S -glycosides ( 89 ) from the reaction of 7-mercapto-4-methyl coumarin ( 50 ) as aromatic thiol acceptors and 4-nitrophenyl-β-D-glucuronide ( p NP-GlcA) ( 88 ) as a sugar donor (glucuronide donor) was reported ( Scheme 32 ) [ 86 ]. The reaction was efficiently glycosylated by Dt GlcA-E396Q (the mutated form of β-D-glucuronidase Dt GlcA) as a biocatalyst with a 51% yield in pKa 5.03 [ 86 ].…”

Biocatalytic Synthesis of Coumarin S-Glycosides: Towards Non-Cytotoxic Probes for Biomedical Imaging and Sensing

“…Derived from retaining GHs, their acid/base residue essential for the hydrolytic activity has been substituted via site-directed mutagenesis with a non-catalytically active amino acid, such as alanine (A), glutamine (Q), or asparagine (N). Following a comparable strategy, our research team has developed a repertoire of thioglycoligases through the selective modification of the active site of several GHs, derived from the thermophilic organism Dictyoglomus thermophilum [ 4 , 16 , 17 , 18 ]. These mutants, characterized by a drastic reduction in their hydrolytic activities due to the replacement of the catalytic residue with either alanine or glutamine, can efficiently catalyze the binding of a specific carbohydrate molecule onto an aromatic thiol, resulting in the synthesis of S -glycoside derivatives with a high yield.…”

“…In the context of this study, 7-mercapto-4-methylcoumarin ( 7-MC ) has been identified as a valuable sugar acceptor [ 17 , 19 , 20 ] ( Figure 1 ). Within the expansive family of coumarins, this compound exhibits the common structure with the benzene ring fused to an α-pyrone moiety.…”