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C5-azobenzene-substituted 2'-deoxyuridine-containing oligodeoxynucleotides for photo-switching hybridization.

ABSTRACT: A new photoisomeric nucleoside dUAz bearing an azobenzene group at the C5-position of 2'-deoxyuridine was designed and synthesized. Photoisomerization of dUAz in oligodeoxynucleotides can be achieved rapidly and selectively with 365 nm (forward) and 450 nm (backward) irradiation. Thermal denaturation experiments revealed that dUAz stabilized the duplex in the cis-form and destabilized it in the trans-form with mismatch discrimination ability comparable to thymidine. These results indicate that dUAz could be a powerful material for reversibly manipulating nucleic acid hybridization with spatiotemporal control.

SUBMITTER: Mori S

PROVIDER: S-EPMC6271114 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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C5-azobenzene-substituted 2'-deoxyuridine-containing oligodeoxynucleotides for photo-switching hybridization.

Mori Shohei S Morihiro Kunihiko K Obika Satoshi S

Molecules (Basel, Switzerland) 20140422 4

A new photoisomeric nucleoside dUAz bearing an azobenzene group at the C5-position of 2'-deoxyuridine was designed and synthesized. Photoisomerization of dUAz in oligodeoxynucleotides can be achieved rapidly and selectively with 365 nm (forward) and 450 nm (backward) irradiation. Thermal denaturation experiments revealed that dUAz stabilized the duplex in the cis-form and destabilized it in the trans-form with mismatch discrimination ability comparable to thymidine. These results indicate that d ...[more]

PMID: 24759071

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Project description:BACKGROUND AND PURPOSE:The photo-isomerizable local anaesthetic, quaternary ammonium-azobenzene-quaternary ammonium (QAQ), provides rapid, optical control over pain signalling without involving genetic modification. In darkness or in green light, trans-QAQ blocks voltage-gated K+ and Na+ channels and silences action potentials in pain-sensing neurons. Upon photo-isomerization to cis with near UV light, QAQ blockade is rapidly relieved, restoring neuronal activity. However, the molecular mechanism of cis and trans QAQ blockade is not known. Moreover, the absorption spectrum of QAQ requires UV light for photo-control, precluding use deep inside neural tissue. EXPERIMENTAL APPROACH:Electrophysiology and molecular modelling were used to characterize the binding of cis and trans QAQ to voltage-gated K+ channels and to develop quaternary ammonium-ethylamine-azobenzene-quaternary ammonium (QENAQ), a red-shifted QAQ derivative controlled with visible light. KEY RESULTS:trans QAQ was sixfold more potent than cis QAQ, in blocking current through Shaker K+ channels. Both isomers were use-dependent, open channel blockers, binding from the cytoplasmic side, but only trans QAQ block was slightly voltage dependent. QENAQ also blocked native K+ and Na+ channels preferentially in the trans state. QENAQ was photo-isomerized to cis with blue light and spontaneously reverted to trans within seconds in darkness, enabling rapid photo-control of action potentials in sensory neurons. CONCLUSIONS AND IMPLICATIONS:Light-switchable local anaesthetics provide a means to non-invasively photo-control pain signalling with high selectivity and fast kinetics. Understanding the mode of action of QAQ and related compounds will help to design of drugs with improved photo-pharmacological properties. LINKED ARTICLES:This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc.

Dataset Information

C5-azobenzene-substituted 2'-deoxyuridine-containing oligodeoxynucleotides for photo-switching hybridization.

Publications

C5-azobenzene-substituted 2'-deoxyuridine-containing oligodeoxynucleotides for photo-switching hybridization.

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