Exploring the synthetic potency of the first furanothioglycoligase through original remote activation

Abstract

Thioglycosidic bonds are of utmost importance in biomolecules as their incorporation led to more stable glycomimetics with potential drug activities. Until now only chemical methods were available for their incorporation into glycofuranosyl conjugates. Herein, we wish to describe the use of the first furanothioglycoligase for the preparation of a great variety of thioaryl derivatives with moderate to excellent yields. Of great interest, a stable 1-thioimidoyl arabinofuranose, classically used in chemical glycosylation, was able to efficiently act as a donor through an original enzymatic remote activation mechanism. Study of the chemical structure as well as the nucleophilicity of the thiol allowed us to optimize this biocatalyzed process. As a consequence, this mutated enzyme constitutes an original, mild and eco-friendly method of thioligation.

Galactofuranosidase from JHA 19 Streptomyces sp.: subcloning and biochemical characterization

“…efficiency ever observed of 14 mM -1 .s -1 . Since to date, only a few furanosidases have been involved in the chemoenzymatic approaches, it would be of great interest to explore and evaluate the potential synthetic ability of this enzyme to act both as wild-type in transglycosylation [29] or after site-directed mutagenesis as an efficient thioligase [30] in the efficient preparation of galactofuranosyl conjugates. Works are currently under progress in this direction and results will be reported in due course.…”

The α‐Thioglycoligase Derived from a GH89 α‐N‐Acetylglucosaminidase Synthesises α‐N‐Acetylglucosamine‐Based Glycosides of Biomedical Interest

“…Reactions were performed at 37 °C using 5 mM 2NP‐α‐GlcNAc as donor in 100 mM sodium phosphate buffer. Based on previous reports that the p K a of the thiol group is an important consideration in its ability to act as acceptor in a thioglycoligase reaction, we chose the thiols to span a range of p K a values, and also performed the reactions at various pHs to evaluate if the predominance of the thiolate anion is a prerequisite for the TGL reaction to proceed. Reactions were evaluated by TLC and scored for product formation and hydrolysis as a side‐reaction (Table ).…”

Synthesis of Glycans and Glycopolymers Through Engineered Enzymes

“…The arabinofuranosidase Ara f 51 from Clostridium thermocellum has recently been transformed into a thioglycoligase, making it the first to function on furanosides . Although this enzyme was unable to function with any of the thiofuranoses synthesized, it was able to utilize aryl thiol acceptors.…”