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Rational Design of Glycomimetic Compounds Targeting the Saccharomyces cerevisiae Transglycosylase Gas2
Author(s) -
Delso Ignacio,
ValeroGonzález Jessika,
Marca Eduardo,
Tejero Tomás,
HurtadoGuerrero Ramón,
Merino Pedro
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12650
Subject(s) - saccharomyces cerevisiae , rational design , chemistry , yeast , biochemistry , docking (animal) , enzyme , stereochemistry , mutant , combinatorial chemistry , biophysics , nanotechnology , biology , materials science , gene , medicine , nursing
The transglycosylase Saccharomyces cerevisiae Gas2 ( Sc Gas2) belongs to a large family of enzymes that are key players in yeast cell wall remodeling. Despite its biologic importance, no studies on the synthesis of substrate‐based compounds as potential inhibitors have been reported. We have synthesized a series of docking‐guided glycomimetics that were evaluated by fluorescence spectroscopy and saturation‐transfer difference ( STD ) NMR experiments, revealing that a minimum of three glucose units linked via a β ‐(1,3) linkage are required for achieving molecular recognition at the binding donor site. The binding mode of our compounds is further supported by STD ‐ NMR experiments using the active site‐mutants Y107Q and Y244Q. Our results are important for both understanding of Sc Gas2–substrate interactions and setting up the basis for future design of glycomimetics as new antifungal agents.