Bioconjugation with Thiols by Benzylic Substitution
Bioconjugation with Thiols by Benzylic Substitution
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DOI：
10.1002/chem.201706149
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发表时间：
2018-03-15
影响因子：
4.3
通讯作者：
Ohshima, Takashi
中科院分区：
文献类型：
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作者：
Watanabe, Kenji;Ohshima, Takashi
3-吲哚基（羟基）乙酸衍生物与硫醇的苄基取代进行具体的氨基，羧基和磷酸基团的存在下，在弱酸性水溶液中，在几乎生理条件下，而没有反应发生在pH值超过7。动力学研究表明，该反应遵循二级动力学（一级反应物和一级硫醇）在对比的S（N）1机制的常见的苄取代醇。本发明的生物大分子功能化方法的实用性使用几种模型蛋白质，如溶菌酶、胰岛素、胰蛋白酶和血清白蛋白来证明。修饰后溶菌酶对溶壁微球菌细胞的催化裂解活性得以保留。
A benzylic substitution of 3-indolyl(hydroxyl)acetate derivatives with thiols proceeded specifically in the presence of amino, carboxy, and phosphate groups in weakly acidic aqueous solutions under nearly physiological condition, while no reaction occurred at pH over 7. Kinetic studies revealed that the reaction followed second-order kinetics (first-order in the reactant and first-order in thiol) in contrast with the S(N)1 mechanism of common benzylic substitution of alcohols. The utility of the present method for functionalization of biomacromolecules was demonstrated using several model proteins, such as lysozyme, insulin, trypsin, and serum albumin. The catalytic bioactivity of lysozyme in lysis of Micrococcus lysodeikticus cells was completely retained after the modification.