文献类型：期刊文献

英文题名：Fluorophore-Promoted Facile Deprotonation and Exocyclic Five-Membered Ring Cyclization for Selective and Dynamic Tracking of Labile Glyoxals

作者：Xu, Huan[1,2];Liu, Qianqian[1,2];Song, Xiaodong[3];Wang, Chao[4];Wang, Xinru[5];Ma, Shengnan[1,2];Wang, Xiaolei[1,2];Feng, Yan[5];Meng, Xiangming[5];Liu, Xiaogang[4];Wang, Wei[1,2,6,7];Lou, Kaiyan[1,2]

机构：[1]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[3]Fudan Univ, Hua Shan Hosp North, Med Lab Dept, Shanghai 201907, Peoples R China;[4]Singapore Univ Technol & Design, Fluorescence Res Grp, Singapore 487372, Singapore;[5]Anhui Univ, Sch Chem & Chem Engn, Hefei 230601, Anhui, Peoples R China;[6]Univ Arizona, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA;[7]Univ Arizona, BIOS Inst, Tucson, AZ 85721 USA

年份：2020

卷号：92

期号：20

起止页码：13829

外文期刊名：ANALYTICAL CHEMISTRY

收录：;EI(收录号：20204809554216);WOS:【SCI-EXPANDED(收录号:WOS:000584418100032)】；

基金：The work was supported by the National Natural Science Foundation of China (Grant Nos. 21577037 and 21738002), the State Key Laboratory of Bioreactor Engineering, Shanghai Natural Science Fund (Grant No. 20ZR1414700), the Shanghai Sailing Program (Grant No. 19YF1412500), the Singapore University of Technology and Design (SUTD), the SUTD-MIT International Design Centre (IDC) (Grant Nos. T1SRCI17126 and IDG31800104), and the SUTD-ZJU Research Collaboration Grant (SD201802). The authors would like to acknowledge the use of the computing service of SUTD-MIT IDC and the National Supercomputing Center, Singapore.

语种：英文

外文关键词：Fluorophores - Formaldehyde - Metabolism - Mass spectrometry - Mammals - Liquid chromatography - Metabolites - Amino acids - Nitric oxide - Complex networks - Modulation - Diagnosis

摘要：The lack of effective chemical tools capable of dynamic tracking of labile glyoxal species (GOS) [e.g., methylglyoxal (MGO) and glyoxal (GO)] levels with high selectivity over other relevant electrophilic species, particularly, formaldehyde (FA) and nitric oxide (NO), has significantly hampered the understanding of their roles in a complex metabolic network and disease progressions. Herein, we report the rational design of the bioinspired 4-(2-guanidino)-1,8-naphthalimide fluorescent probes NAP-DCP-1 and NAP-DCP-3 from arginine-specific protein modifications. These probes undergo facile reversible fluorophore-promoted deprotonation-cyclization of a guanidium ion with labile GOS to form exocyclic five-membered dihydroxyimidazolidines. The probe NAP-DCP-1 can differentiate GOS levels in the serum of diabetic mice and patients from nondiabetic ones, which correlate very well with glucose levels, providing the GOS level as a potential new biomarker for diabetes diagnosis. Notably, the endoplasmic reticulum (ER)-targeting probe NAP-DCP-3 enabled the study of GOS perturbation in ER under various stress conditions and led to the discovery that formaldehyde (FA), either exogenously added or endogenously generated, could induce GOS level increases in ER. This finding reveals the previous unknown connection of FA with upregulated GOS levels and suggests that GOS is a key metabolite in bridging one-carbon metabolism with glycolysis and the downstream cell redox status. Moreover, the probes also showed potentials in separate quantification of MGO and GO via ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and unexpected selectivity modulation for GO over MGO via two-photon excitation. It is expected that probes reported herein provide powerful tools to study GOS level modulations in complex biological networks and would facilitate GOS-associated basic research and discovery.