真菌天冬氨酸半醛脱氢酶高效共价失活剂的开发
Development of Efficient Covalent Inactivators of a Fungal Aspartate Semialdehyde Dehydrogenase.
作者信息
Friday Samantha N, Koellner Liezel A, Brown Spencer W, Calbat Christopher N, Curran Catherine F, Dietz Jordan D, Koenig-Dummer Andreas, Friday Paul D, Parker James A, Simmons Noah A, Urmey Finnean A, West Alexis N, Zagler Sebastian G, Viola Ronald E, Halkides Christopher J
机构信息
Department of Chemistry and Biochemistry, University of Toledo, Toledo, Ohio, USA.
Department of Chemistry and Biochemistry, University of North Carolina Wilmington, Wilmington, North Carolina, USA.
出版信息
Drug Dev Res. 2025 May;86(3):e70095. doi: 10.1002/ddr.70095.
Aspartate semialdehyde dehydrogenase (ASADH) catalyzes the second step in the fungal pathway towards the synthesis of threonine, isoleucine, and methionine, and it has been identified as a viable target for antifungal drug development. Our previous work produced a group of vinyl sulfones that function as irreversible covalent inactivators of this enzyme. We have now expanded this initial set to produce vinyl sulfones with higher kinetic efficiency as covalent inactivators of ASADH purified from the pathogenic fungal species Candida albicans. The catalytic efficiency of these inactivators has also been compared to related classes of irreversible inactivators, vinyl sulfonamides, acrylamides, and sulfonyl ketones.
天冬氨酸半醛脱氢酶（ASADH）催化真菌中通向苏氨酸、异亮氨酸和蛋氨酸合成途径的第二步反应，并且它已被确定为抗真菌药物开发的一个可行靶点。我们之前的工作制备了一组乙烯基砜，它们可作为该酶的不可逆共价失活剂。现在，我们已扩展了这一初始系列，以制备具有更高动力学效率的乙烯基砜，作为从致病性真菌白色念珠菌中纯化出的ASADH的共价失活剂。这些失活剂的催化效率也已与相关类别的不可逆失活剂，即乙烯基磺酰胺、丙烯酰胺和磺酰基酮进行了比较。
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