Iminoboronates are efficient intermediates for selective, rapid and reversible N-terminal cysteine functionalisation.
Iminoboronates are efficient intermediates for selective, rapid and reversible N-terminal cysteine functionalisation.
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DOI：
10.1039/c6sc01520d
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发表时间：
2016-08-01
期刊：
影响因子：
8.4
通讯作者：
Gois PMP
中科院分区：
文献类型：
--
作者：
Faustino H;Silva MJSA;Veiros LF;Bernardes GJL;Gois PMP
甲酰基苯硼酸快速和选择性地与N-末端半胱氨酸反应，产生可逆的硼化噻唑烷，其可用于肽的相互作用正交修饰。我们发现，甲酰基苯硼酸（2FBBA）选择性地与N-末端半胱氨酸反应，产生具有B-N键的硼化噻唑烷。该反应在温和的水溶液条件下（pH 7.4，23 °C）表现出非常快的恒定速率（2.38 ± 0.23 × 102 M-1 s-1），并耐受N-半胱氨酸相邻位置的不同氨基酸。DFT计算强调了这种连接反应的非对映选择性性质，并支持近端硼酸参与亚胺官能团的活化和通过螯合作用稳定硼化噻唑烷。2FBBA试剂允许模型肽（C-卵清蛋白和层粘连蛋白片段）的有效官能化，并且硼化噻唑烷构建体显示出随时间稳定，尽管反应在苄基羟胺存在下是可逆的。该反应被证明是高度化学选择性的，2FBBA被用来官能化的N-末端半胱氨酸的降钙素在一个潜在的竞争链中硫醇基团的存在下。当2FBBA与传统的马来酰亚胺化学结合时，这种精致的选择性特征使得降钙素的双重功能化和这种肽的相互作用正交修饰成为可能。这些结果突出了这种方法构建复杂和明确定义的生物缀合物的潜力。
Formyl benzeno boronic acids rapidly and selectively react with N-terminal cysteines to yield a reversible boronated thiazolidine that may be used in the interactive orthogonal modification of peptides. We show that formyl benzeno boronic acids (2FBBA) selectively react with N-terminal cysteines to yield a boronated thiazolidine featuring a B–N bond. The reaction exhibits a very rapid constant rate (2.38 ± 0.23 × 102 M–1 s–1) under mild aqueous conditions (pH 7.4, 23 °C) and tolerates different amino acids at the position adjacent to the N-cysteine. DFT calculations highlighted the diastereoselective nature of this ligation reaction and support the involvement of the proximal boronic acid in the activation of the imine functionality and the stabilisation of the boronated thiazolidine through a chelate effect. The 2FBBA reagent allowed the effective functionalisation of model peptides (C-ovalbumin and a laminin fragment) and the boronated thiazolidine construct was shown to be stable over time, though the reaction was reversible in the presence of benzyl hydroxylamine. The reaction proved to be highly chemoselective, and 2FBBA was used to functionalize the N-terminal cysteine of calcitonin in the presence of a potentially competing in-chain thiol group. This exquisite selectivity profile enabled the dual functionalisation of calcitonin and the interactive orthogonal modification of this peptide when 2FBBA was combined with conventional maleimide chemistry. These results highlight the potential of this methodology to construct complex and well-defined bioconjugates.
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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：
18.3
作者：
Ngo, John T.;Tirrell, David A.
通讯作者：
Tirrell, David A.
影响因子：
21.8
作者：
Krall, Nikolaus;da Cruz, Filipa P.;Bernardes, Goncalo J. L.
通讯作者：
Bernardes, Goncalo J. L.
影响因子：
56.9
作者：
DAWSON, PE;MUIR, TW;KENT, SBH
通讯作者：
KENT, SBH
影响因子：
15
作者：
Casi, Giulio;Huguenin-Dezot, Nicolas;Neri, Dario
通讯作者：
Neri, Dario