Dual-Boronic Acid Reagents That Combine Dynamic and Covalent Bioconjugation
Dual-Boronic Acid Reagents That Combine Dynamic and Covalent Bioconjugation
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结合动态和共价生物共轭的双硼酸试剂
DOI：
10.1021/acs.bioconjchem.2c00508
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发表时间：
2022
影响因子：
4.7
通讯作者：
Ball, Zachary T.
中科院分区：
文献类型：
--
作者：
Swierczynski, Michael J.;Ding, Yuxuan;Ball, Zachary T.
硼酸和硼酸酯在化学生物学中有重要用途。含有正交硼酸对的分子可用于顺序的金属催化的交叉偶联，以便于制备复杂的生物缀合物，包括蛋白质-蛋白质缀合物。在本文中，我们扩展了双硼酸试剂串联共价和动态生物共轭。2-硝基芳基硼酸与半胱氨酸残基的顺序交叉偶联和苯基硼酸与水杨基异羟肟酸（SHA）的缩合在生理条件下容易地提供具有双共价键和动态键的生物缀合物。小分子-和大分子-蛋白质缀合物都适用于这种方法，并且在加入过量的未官能化SHA或活性氧物质后是可逆的。这些调查提供了新的见解SHA加合物的动力学稳定性。
Boronic acids and boronate esters find appreciable use in chemical biology. Molecules containing orthogonal boronic acid pairs can be utilized for sequential metal-catalyzed cross-couplings for facile preparation of complex bioconjugates including protein-protein conjugates. In this paper, we expand bis-boronic acid reagents for tandem covalent and dynamic bioconjugation. Sequential cross-coupling of 2-nitroarylboronic acid with cysteine residues and condensation of phenylboronic acid with salicylhydroxamic acids (SHA) readily afforded bioconjugates under physiological conditions with dual covalent and dynamic linkages. Both small molecule– and macromolecule–protein conjugates were amenable with this approach and reversible upon addition of excess unfunctionalized SHA or reactive oxygen species. These investigations provide new insights into the kinetic stability of SHA adducts.