2024-03-28T14:08:50Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1226102020-05-11T08:58:50Zcom_10261_31com_10261_3com_10261_52707com_10261_5com_10261_34col_10261_284col_10261_52708col_10261_287
00925njm 22002777a 4500
dc
Delso, J. Ignacio
author
Valero-González, Jessika
author
Marca, Eduardo
author
Tejero, Tomás
author
Hurtado-Guerrero, Ramón
author
Merino, Pedro
author
2016
The transglycosylase Saccharomyces cerevisiae Gas2 (ScGas2) belongs to a large family of enzymes that are key players in yeast cell wall remodeling. Despite its biological 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 ScGas2-substrate interactions and setting up the basis for future design of glycomimetics as new antifungal agents.
Chemical Biology and Drug Design 87(2): 163-170 (2016)
1747-0277
http://hdl.handle.net/10261/122610
10.1111/cbdd.12650
1747-0285
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100003176
http://dx.doi.org/10.13039/501100010067
Transglycosylase
Glycomimetics
STD-NMR
Docking
Carbohydrates
Rational design of glycomimetic compounds targeting the Saccharomyces cerevisiae transglycosylase Gas2