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Download fileSanger’s Reagent Sensitized Photocleavage of Amide Bond for Constructing Photocages and Regulation of Biological Functions
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posted on 2021-06-30, 13:06 authored by Tingwen Wei, Sheng Lu, Jiahui Sun, Zhijun Xu, Xiao Yang, Fang Wang, Yang Ma, Yun Stone Shi, Xiaoqiang ChenPhotolabile groups offer promising tools to study biological processes
with high spatial and temporal control. In the investigation, we designed
and prepared several new glycine amide derivatives of Sanger’s
reagent and demonstrated that they serve as a new class of photocages
for Zn2+ and an acetylcholinesterase (AChE) inhibitor.
We showed that the mechanism for photocleavage of these substances
involves initial light-driven cyclization between the 2,4-dinitrophenyl
and glycine methylene groups to form acyl benzimidazole N-oxides, which undergo secondary photoinduced decarboxylation in
association with rupture of an amide bond. The cleavage reactions
proceed with modest to high quantum yields. We demonstrated that these
derivatives can be used in targeted intracellular delivery of Zn2+, fluorescent imaging by light-triggered Zn2+ release,
and regulation of biological processes including the enzymatic activity
of carbonic anhydrase (CA), negative regulation of N-methyl-d-aspartate receptors (NMDARs), and pulse rate of
cardiomyocytes. The successful proof-of-concept examples described
above open a new avenue for using Sanger’s reagent-based glycine
amides as photocages for the exploration of complex cellular functions
and signaling pathways.
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Amide Bondmethyl-d-aspartate receptorsintracellular deliveryproof-of-concept examplesSangeramide bondphotocageNMDARConstructing Photocageslight-driven cyclizationBiological Functions Photolabile gr...Znform acyl benzimidazole Nglycine methylene groupsquantum yieldscleavage reactionsregulationCAcarbonic anhydrasephotoinduced decarboxylationpulse rateglycine amide derivatives