Formation of hydrazones and stabilized boron-nitrogen heterocycles in aqueous solution from carbohydrazides and ortho-formylphenylboronic acids.
Formation of hydrazones and stabilized boron-nitrogen heterocycles in aqueous solution from carbohydrazides and ortho-formylphenylboronic acids.
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DOI：
10.1039/c7ob01708a
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发表时间：
2017-09-20
影响因子：
3.2
通讯作者：
Bane S
中科院分区：
文献类型：
--
作者：
Gu H;Chio TI;Lei Z;Staples RJ;Hirschi JS;Bane S
最近除了一套快速生物正交反应结合肼和羟胺与邻羰基取代的苯基硼酸。碳酰肼很容易被掺入到生物分子中，因此可能是这些反应中有吸引力的伙伴。在这里，我们表明，简单的烷基碳酰肼形成一个单一的产品与邻甲酰基苯硼酸在有机溶剂和固体状态。然而，由碳酰肼在缓冲水溶液中形成的产物的溶液结构与在有机溶剂和固态中鉴定的那些明显不同。反应物形成的混合物的腙和杂环的产品，其相对组成随pH值而变化。所观察到的可逆性bioconguates使用碳酰肼，因此可以解释的可逆性的硼-氮键中的杂环。相反，在碳酰肼底物中包含α-胺产生单一产物，其中两个氮键合到硼上。这些三环结构在pH 4至pH 9的有机溶剂、固态和水溶液中相同。与α -氨基碳酰肼形成的生物缀合物对SDS-PAGE稳定，而与简单烷基碳酰肼形成的生物缀合物则不稳定。我们提出，在碳氢化物底物中包含分子内稳定配体是一个普遍适用的原则，可以利用它来形成具有确定结构和耐水解性的硼酸基生物缀合物。
A recent addition to the suite of fast bioorthogonal reactions combines hydrazine and hydroxylamines with ortho-carbonyl substituted phenylboronic acids. Carbohydrazides are easily incorporated into biomolecules and are therefore may be attractive partners in these reaction. Here we show that simple alkyl carbohydrazides form a single product with ortho-formylphenylboronic acid in organic solvent and in solid state. The solution structures of the products formed from the carbohydrazides in buffered aqueous solution, however, are markedly different than those identified in organic solvent and solid state. The reactants form a mixture of hydrazone and heterocylic products, the relative composition of which varies with pH. The observed reversibility of bioconguates using carbohydrazide can thus be explained by the reversibility of the boron-nitrogen bond in the heterocycle. In contrast, inclusion of an α-amine to the carbohydrazide substrate yields a single product in which both nitrogens are bonded to boron. These tricyclic structures are the same in organic solvent, solid state and aqueous solution from pH 4 to pH 9. Bioconjugates formed with α -amino carbohydrazides are stable to SDS-PAGE, while those formed with simple alkyl carboyhydrazides are not. We propose that includion of an intramolecular stabilizing ligand in a carbohydride substrate is a generally applicable principle that may be exploited to form boronic acid-based bioconjugates with defined structure and resistance to hydrolysis.
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DOI：
10.1002/chem.201502077
发表时间：
2015-10-12
期刊：
Chemistry (Weinheim an der Bergstrasse, Germany)
影响因子：
--
作者：
Bandyopadhyay A;Gao J
通讯作者：
Gao J
影响因子：
4.7
作者：
Thom, Jennifer;Anderson, David;Cotton, Graham
通讯作者：
Cotton, Graham
影响因子：
15
作者：
Bandyopadhyay A;Cambray S;Gao J
通讯作者：
Gao J
使用分选酶对蛋白质进行不可逆位点特异性肼解
影响因子：
16.6
作者：
Li, Yi-Ming;Li, Yi-Tong;Liu, Lei
通讯作者：
Liu, Lei
影响因子：
8.4
作者：
Schmidt, Pascal;Stress, Cedric;Gillingham, Dennis
通讯作者：
Gillingham, Dennis