title: Photoregulating RNA digestion using azobenzene linked dumbbell antisense oligodeoxynucleotides.
abstract: Introduction of 4,4'-bis(hydroxymethyl)-azobenzene (azo) to dumbbell hairpin oligonucleotides at the loop position was able to reversibly control the stability of the whole hairpin structure via UV or visible light irradiation. Here, we designed and synthesized a series of azobenzene linked dumbbell antisense oligodeoxynucleotides (asODNs) containing two terminal hairpins that are composed of an asODN and a short inhibitory sense strand. Thermal melting studies of these azobenzene linked dumbbell asODNs indicated that efficient trans to cis photoisomerization of azobenzene moieties induced large difference in thermal stability (ΔTm = 12.1-21.3 °C). In addition, photomodulation of their RNA binding abilities and RNA digestion by RNase H was investigated. The trans-azobenzene linked asODNs with the optimized base pairs between asODN strands and inhibitory sense strands could only bind few percentage of the target RNA, while it was able to recover their binding to the target RNA and degrade it by RNase H after light irradiation. Upon optimization, it is promising to use these azobenzene linked asODNs for reversible spatial and temporal regulation of antisense activities based on both steric binding and RNA digestion by RNase H.
authors.affiliation: †School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China.|‡State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.affiliation: †School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China.|‡State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Yujian
authors.initials: Y
authors.lastname: He
authors.affiliation: ‡State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xinjing
authors.initials: X
authors.lastname: Tang
mesh_terms: D001391:Azo Compounds / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D004926:Escherichia coli / Q000201:enzymology*; D007536:Isomerism; D008027:Light; D009690:Nucleic Acid Conformation; D020319:Oligodeoxyribonucleotides, Antisense / Q000737:chemistry / Q000378:metabolism*; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D016914:Ribonuclease H / Q000378:metabolism*; D013816:Thermodynamics; D014466:Ultraviolet Rays
chemical_list: D001391:Azo Compounds; D020319:Oligodeoxyribonucleotides, Antisense; D012313:RNA; D016914:Ribonuclease H; C009850:azobenzene