气候变化领域集成服务门户(CCPortal): Boronic acid with high oxidative stability and utility in biological contexts

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DOI	10.1073/pnas.2013691118
	Boronic acid with high oxidative stability and utility in biological contexts
	Graham B.J.; Windsor I.W.; Gold B.; Raines R.T.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	Despite their desirable attributes, boronic acids have had a minimal impact in biological contexts. A significant problem has been their oxidative instability. At physiological pH, phenylboronic acid and its boronate esters are oxidized by reactive oxygen species at rates comparable to those of thiols. After considering the mechanism and kinetics of the oxidation reaction, we reasoned that diminishing electron density on boron could enhance oxidative stability. We found that a boralactone, in which a carboxyl group serves as an intramolecular ligand for the boron, increases stability by 104-fold. Computational analyses revealed that the resistance to oxidation arises from diminished stabilization of the p orbital of boron that develops in the rate-limiting transition state of the oxidation reaction. Like simple boronic acids and boronate esters, a boralactone binds covalently and reversibly to 1,2-diols such as those in saccharides. The kinetic stability of its complexes is, however, at least 20-fold greater. A boralactone also binds covalently to a serine side chain in a protein. These attributes confer unprecedented utility upon boralactones in the realms of chemical biology and medicinal chemistry. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Bioisosteres; Boronic acid; Oxidative stability; Pharmacophore; Stereoelectronic effects
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180407
作者单位	Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, United States
推荐引用方式 GB/T 7714	Graham B.J.,Windsor I.W.,Gold B.,et al. Boronic acid with high oxidative stability and utility in biological contexts[J],2021,118(10).
APA	Graham B.J.,Windsor I.W.,Gold B.,&Raines R.T..(2021).Boronic acid with high oxidative stability and utility in biological contexts.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Graham B.J.,et al."Boronic acid with high oxidative stability and utility in biological contexts".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).