title: Combinatorial Strategy to Identify Fluorescent Probes for Biothiol and Thiophenol Based on Diversified Pyrimidine Moieties and Their Biological Applications.
abstract: We present a feasible paradigm of developing original fluorescent probes for target biomolecules via combinatorial chemistry. In this developmental program, pyrimidine moieties were investigated and optimized as unique recognition units for thiols for the first time through a parallel synthesis in combination with a rapid screening process. This time-efficient and cost-saving process effectively facilitated the developmental progress and provided detailed structure-reactivity relationships. As a result, Res-Biot and Flu-Pht were identified as optimal fluorescent probes for biothiol and thiophenol, respectively. Their favorable characteristics and superior applicability have been well demonstrated in both chemical and biological contexts. In particular, Res-Biot enables the direct visualization of biothiol fluctuations during oxidative stress and cell apoptosis, indicating its suitability in elucidation of a specific pathophysiological process in both living cells and living animals. Meanwhile, Flu-Pht is competent to visualize thiophenols without the interference from endogenous biothiols in living cells.
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Molecular and Nano Science, Shandong Normal University , Jinan 250014, P. R. China.
authors.forename: Xilei
authors.initials: X
authors.lastname: Xie
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Molecular and Nano Science, Shandong Normal University , Jinan 250014, P. R. China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Li
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Molecular and Nano Science, Shandong Normal University , Jinan 250014, P. R. China.
authors.forename: Fuyan
authors.initials: F
authors.lastname: Tang
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Molecular and Nano Science, Shandong Normal University , Jinan 250014, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 10050, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Molecular and Nano Science, Shandong Normal University , Jinan 250014, P. R. China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Jiao
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Molecular and Nano Science, Shandong Normal University , Jinan 250014, P. R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Molecular and Nano Science, Shandong Normal University , Jinan 250014, P. R. China.
authors.forename: Bo
authors.identifier: 0000-0002-8712-7025
authors.initials: B
authors.lastname: Tang
mesh_terms: D000818:Animals; D003545:Cysteine / Q000032:analysis; D005456:Fluorescent Dyes / Q000737:chemistry*; D005978:Glutathione / Q000032:analysis; D006367:HeLa Cells; D056945:Hep G2 Cells; D006710:Homocysteine / Q000032:analysis; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D061848:Optical Imaging; D010636:Phenols / Q000032:analysis* / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000032:analysis* / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D010636:Phenols; D011743:Pyrimidines; D013438:Sulfhydryl Compounds; D006710:Homocysteine; C042983:thiophenol; D005978:Glutathione; D003545:Cysteine