致力于开发新型光不稳定保护基团，使其在可见光光解时能快速释放生物活性化合物。

Toward the development of new photolabile protecting groups that can rapidly release bioactive compounds upon photolysis with visible light.

作者信息

Banerjee Anamitro, Grewer Christof, Ramakrishnan Latha, Jäger Jürgen, Gameiro Armanda, Breitinger Hans-Georg A, Gee Kyle R, Carpenter Barry K, Hess George P

机构信息

Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.

出版信息

J Org Chem. 2003 Oct 31;68(22):8361-7. doi: 10.1021/jo0300643.

DOI:10.1021/jo0300643

PMID:14575458

Abstract

The synthesis and characterization of a new photolabile protecting group (caging group) for carboxylic acids, the 2-(dimethylamino)-5-nitrophenyl (DANP) group, is described. This compound has a major absorption band in the visible wavelength region with a maximum near 400 nm (epsilon400 = 9077 M(-1) cm(-1) at pH 7.4 and 21 degrees C). The caging group is attached through an ester linkage to the carboxyl functionality of beta-alanine, which activates the inhibitory glycine receptor in the mammalian central nervous system. Such caged compounds play an important role in transient kinetic investigations of fast cellular processes. Upon photolysis of DANP-caged beta-alanine, the caging group is released within 5 micros. Quantum yields of 0.03 and 0.002 were obtained in the UV region (308 and 360 nm) and the visible region (450 nm), respectively. Laser-pulse photolysis experiments, using 337 or 360 nm light, were performed with the caged compound equilibrated with HEK 293 cells transiently transfected with cDNA encoding the alpha1 homomeric, wild-type glycine receptor. The experiments demonstrated that neither DANP-caged beta-alanine nor its byproducts inhibit or activate the glycine receptors on the cell surface. Under physiological conditions, the DANP-caged beta-alanine is water-soluble and stable and can be used for transient kinetic measurements.

摘要

本文描述了一种新型的用于羧酸的光不稳定保护基（笼蔽基团）——2-(二甲基氨基)-5-硝基苯基（DANP）基团的合成与表征。该化合物在可见光波长区域有一个主要吸收带，最大吸收峰接近400 nm（在pH 7.4和21℃时，ε400 = 9077 M⁻¹ cm⁻¹）。笼蔽基团通过酯键连接到β-丙氨酸的羧基官能团上，β-丙氨酸可激活哺乳动物中枢神经系统中的抑制性甘氨酸受体。这类笼蔽化合物在快速细胞过程的瞬态动力学研究中起着重要作用。DANP笼蔽的β-丙氨酸经光解后，笼蔽基团在5微秒内释放。在紫外区域（308和360 nm）和可见光区域（450 nm）分别获得了0.03和0.002的量子产率。使用337或360 nm光进行激光脉冲光解实验，所用的笼蔽化合物与瞬时转染了编码α1同聚体野生型甘氨酸受体cDNA的HEK 293细胞达到平衡。实验表明，DANP笼蔽的β-丙氨酸及其副产物均不会抑制或激活细胞表面的甘氨酸受体。在生理条件下，DANP笼蔽的β-丙氨酸可溶于水且稳定，可用于瞬态动力学测量。