Narayanan Arjun, Jones Lyn H
Chemical Biology Group , BioTherapeutics Chemistry , WorldWide Medicinal Chemistry , Pfizer , 610 Main Street , Cambridge , MA 02139 , USA . Email:
Chem Sci. 2015 May 1;6(5):2650-2659. doi: 10.1039/c5sc00408j. Epub 2015 Mar 16.
Sulfonyl fluoride electrophiles have found significant utility as reactive probes in chemical biology and molecular pharmacology. As warheads they possess the right balance of biocompatibility (including aqueous stability) and protein reactivity. Their functionality is privileged in this regard as they are known to modify not only reactive serines (resulting in their common use as protease inhibitors), but also context-specific threonine, lysine, tyrosine, cysteine and histidine residues. This review describes the application of sulfonyl fluoride probes across various areas of research and explores new approaches that could further enhance the chemical biology toolkit. We believe that sulfonyl fluoride probes will find greater utility in areas such as covalent enzyme inhibition, target identification and validation, and the mapping of enzyme binding sites, substrates and protein-protein interactions.
磺酰氟亲电试剂在化学生物学和分子药理学中作为反应性探针具有显著的实用性。作为弹头，它们在生物相容性（包括水稳定性）和蛋白质反应性之间具有恰当的平衡。在这方面，它们的功能具有独特优势，因为已知它们不仅能修饰活性丝氨酸（因此常用于蛋白酶抑制剂），还能修饰特定环境下的苏氨酸、赖氨酸、酪氨酸、半胱氨酸和组氨酸残基。本综述描述了磺酰氟探针在各个研究领域的应用，并探索了可进一步增强化学生物学工具集的新方法。我们相信磺酰氟探针将在共价酶抑制、靶点鉴定与验证以及酶结合位点、底物和蛋白质 - 蛋白质相互作用图谱绘制等领域发挥更大的作用。
