title: Small-Molecule-Triggered and Light-Controlled Reversible Regulation of Enzymatic Activity.
abstract: The fine control of enzyme activity is essential for the regulation of many important cellular and organismal functions. The light-regulation of proteins serves as an important method for the spatiotemporal control over the production and degradation of an enzyme product. This area is of intense interest for researchers. To the best of our knowledge, the use of small molecules as light-triggered molecular switches to reversibly control enzyme activity at the protein level has not yet been studied. In the present study, we demonstrate the light-controlled reversible regulation of the enzyme using a small-molecule-triggered switch, which is based on molecular recognition between an azobenzene derivative and telomere DNA. This molecule interconverts between the trans and cis states under alternate 365 nm UV and visible light irradiation, which consequently triggers the compaction and extension of telomere DNA. We further provide direct evidence for this structural switch using a circular dichroism study. Furthermore, our strategy has been successfully used to effectively control blood clotting in human plasma.
authors.affiliation: College of Chemistry and Molecular Sciences, Institute of Advanced Studies, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University , Wuhan 430072, Hubei Province, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: College of Chemistry and Molecular Sciences, Institute of Advanced Studies, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University , Wuhan 430072, Hubei Province, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Song
authors.affiliation: College of Chemistry and Molecular Sciences, Institute of Advanced Studies, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University , Wuhan 430072, Hubei Province, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Chemistry and Molecular Sciences, Institute of Advanced Studies, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University , Wuhan 430072, Hubei Province, China.
authors.forename: Boshi
authors.initials: B
authors.lastname: Fu
authors.affiliation: College of Chemistry and Molecular Sciences, Institute of Advanced Studies, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University , Wuhan 430072, Hubei Province, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: He
authors.affiliation: Zhongnan Hospital, Wuhan University , Wuhan 430071, Hubei Province, China.
authors.forename: Xianqun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Zhongnan Hospital, Wuhan University , Wuhan 430071, Hubei Province, China.
authors.forename: Anling
authors.initials: A
authors.lastname: Li
authors.affiliation: Zhongnan Hospital, Wuhan University , Wuhan 430071, Hubei Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: College of Chemistry and Molecular Sciences, Institute of Advanced Studies, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University , Wuhan 430072, Hubei Province, China.
authors.forename: Shaoru
authors.initials: S
authors.lastname: Wang
authors.affiliation: College of Chemistry and Molecular Sciences, Institute of Advanced Studies, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University , Wuhan 430072, Hubei Province, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
mesh_terms: D001391:Azo Compounds / Q000737:chemistry / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008027:Light; D015394:Molecular Structure; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D016615:Telomere / Q000737:chemistry / Q000378:metabolism; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001391:Azo Compounds; D054852:Small Molecule Libraries; D004247:DNA; D013917:Thrombin; C009850:azobenzene