Maza Johnathan C, Howard Christina A, Vipani Megha A, Travis Christopher R, Young Douglas D
Department of Chemistry, College of William & Mary, P.O. Box 8795, Williamsburg, VA 23187, USA.
Department of Chemistry, College of William & Mary, P.O. Box 8795, Williamsburg, VA 23187, USA.
Bioorg Med Chem Lett. 2017 Jan 1;27(1):30-33. doi: 10.1016/j.bmcl.2016.11.041. Epub 2016 Nov 16.
The ability to introduce or modify protein function has widespread application to multiple scientific disciplines. The introduction of unique unnatural amino acids represents an excellent mechanism to incorporate new functionality; however, this approach is limited by ability of the translational machinery to recognize and incorporate the chemical moiety. To overcome this potential limitation, we aimed to exploit the functionality of existing unnatural amino acids to perform bioorthogonal reactions to introduce the desired protein modification, altering its function. Specifically, via the introduction of a terminal alkyne containing unnatural amino acid, we demonstrated chemically programmable protein modification through the Glaser-Hay coupling to other terminal alkynes, altering the function of a protein. In a proof-of-concept experiment, this approach has been utilized to modify the fluorescence spectrum of green fluorescent protein.
引入或修改蛋白质功能的能力在多个科学学科中有着广泛的应用。引入独特的非天然氨基酸是纳入新功能的一种出色机制；然而，这种方法受到翻译机制识别和纳入化学部分能力的限制。为了克服这一潜在限制，我们旨在利用现有非天然氨基酸的功能进行生物正交反应，以引入所需的蛋白质修饰，从而改变其功能。具体而言，通过引入含有末端炔烃的非天然氨基酸，我们展示了通过格拉泽-海偶联与其他末端炔烃进行化学可编程的蛋白质修饰，从而改变蛋白质的功能。在一个概念验证实验中，这种方法已被用于修饰绿色荧光蛋白的荧光光谱。
