Optochemical Control of Biological Processes in Cells and Animals

Ankenbruck, Nicholas; Courtney, Taylor; Naro, Yuta; Deiters, Alexander

doi:10.1002/anie.201700171

Cited by 374 publications

(342 citation statements)

References 374 publications

(518 reference statements)

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“…The current psCID system uses blue light, which is limited in tissue penetration. However,itisalso possible to use other photolabile moieties,s uch as twophoton caging groups, [16] which would shift the PA and PD light to longer wavelengths thus facilitating chemooptogenetic control in living organisms.…”

Section: Tunable and Photoswitchable Chemically Induced Dimerizationfmentioning

confidence: 99%

Tunable and Photoswitchable Chemically Induced Dimerization for Chemo‐optogenetic Control of Protein and Organelle Positioning

Chen

2018

Angewandte Chemie

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The spatiotemporal dynamics of proteins and organelles play an important role in controlling diverse cellular processes. Optogenetic tools using photosensitive proteins and chemically induced dimerization (CID), which allow control of protein dimerization, have been used to elucidate the dynamics of biological systems and to dissect the complicated biological regulatory networks. However, the inherent limitations of current optogenetic and CID systems remain a significant challenge for the fine‐tuning of cellular activity at precise times and locations. Herein, we present a novel chemo‐optogenetic approach, photoswitchable chemically induced dimerization (psCID), for controlling cellular function by using blue light in a rapid and reversible manner. Moreover, psCID is tunable; that is, the dimerization and dedimerization degrees can be fine‐tuned by applying different doses of illumination. Using this approach, we control the localization of proteins and positioning of organelles in live cells with high spatial (μm) and temporal (ms) precision.

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Section: Tunable and Photoswitchable Chemically Induced Dimerizationfmentioning

confidence: 99%

Tunable and Photoswitchable Chemically Induced Dimerization for Chemo‐optogenetic Control of Protein and Organelle Positioning

Chen

2018

Angewandte Chemie

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“…However, as soon as it was possible to follow intracellular events (see above), the necessity arose to manipulate events in single cells and with high temporal resolution. As with imaging, the first solution to the problem was using light ,. In fact, standard protecting group chemistry was modified to be useful in cells, namely by employing a photochemical reaction to remove a blocking group, the so‐called “caging group,” by a flash of light.…”

Section: Introductionmentioning

confidence: 99%

The Life Science Toolbox Provided by Chemical Biology

Schultz

2019

Israel Journal of Chemistry

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This perspective covers a fraction of the diverse engineering branches of chemical biology. Long before the term chemical biology was created, there was the desire to use chemistry for unraveling the endlessly complex world of biology. The impact of this work has been tremendous, as we are now able to follow and switch biological processes at will and in realtime. In fact, without these tools it will be very difficult to address the complexity of biology in the future.

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“…[8,[12][13][14][15][16] Driven by the growing importance of DNAmethylation in biomedical research, there is as trong interest to experimentally lower or increase methylation levels [17][18][19][20][21][22][23] to study,f or example,t he role of epigenetic reprogramming in tissue development or regenerative medicine. [32] Yet, despite the importance of DNAm ethylation in biology, no light-tuneable small-molecule tool has been developed to manipulate methylation levels in cells. Often, the approach is implemented with photosensitive small molecules of tuneable bioactivity.…”

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confidence: 99%

A Photo‐responsive Small‐Molecule Approach for the Opto‐epigenetic Modulation of DNA Methylation

et al. 2019

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Controlling the functional dynamics of DNAwithin living cells is essential in biomedical research. Epigenetic modifications such as DNAmethylation play akey role in this endeavour.D NA methylation can be controlled by genetic means.Y et there are few chemical tools available for the spatial and temporal modulation of this modification. Herein, we present as mall-molecule approach to modulate DNAm ethylation with light. The strategy uses aphoto-tuneable version of ac linically used drug (5-aza-2'-deoxycytidine) to alter the catalytic activity of DNAmethyltransferases,the enzymes that methylate DNA. After uptake by cells,t he photo-regulated molecule can be light-controlled to reduce genome-wide DNA methylation levels in proliferating cells.T he chemical tool complements genetic,b iochemical, and pharmacological approaches to study the role of DNAm ethylation in biology and medicine.The methylation of DNAatposition 5ofcytosine residues is chemically av ery simple but biologically one of the most important modifications of DNA. It influences many biological processes in humans such as the regulation of cell function, cellular reprogramming,a nd organismal development. [1][2][3][4][5][6][7] Biological effects of higher methylation levels at promoters are mediated by lowering the transcription of genes either by blocking the binding of transcription factors or by recruiting unique methyl-recognizing proteins that lower gene expression. Altered levels of methylation are also associated with several diseases [8][9][10][11] including cancer. [8,[12][13][14][15][16] Driven by the growing importance of DNAmethylation in biomedical research, there is as trong interest to experimentally lower or increase methylation levels [17][18][19][20][21][22][23] to study,f or example,t he role of epigenetic reprogramming in tissue development or regenerative medicine. [24,25] Optical control is of particular relevance given the high spatial and temporal resolution of light. Often, the approach is implemented with photosensitive small molecules of tuneable bioactivity. [26][27][28][29][30][31] These can be used without the need for genetic engineering of cells leading to powerful applications within cell biology. [32] Yet, despite the importance of DNAm ethylation in biology, no light-tuneable small-molecule tool has been developed to manipulate methylation levels in cells.Herein, we present ap hoto-mediated small-molecule strategy that modulates methylation in light-exposed cells. At the approachsc entre is an inhibitor that interferes with DNAmethyltransferases (DNMTs), the enzymes responsible for DNAm ethylation [33] including the maintenance DNA methyltransferase 1( DNMT1). [34] Thei nhibitorsb ioactivity becomes tuneable with light by the chemical derivatization with ap hotocage.A ss chematically illustrated in Figure 1a, the attached photocage renders the inhibitor biologically inactive.However, light exposure cleaves off the photocage to restore the original inhibitory effect (Figure 1a). Thep hotocaged molecule is hence expected...

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Optochemical Control of Biological Processes in Cells and Animals

Cited by 374 publications

References 374 publications

Tunable and Photoswitchable Chemically Induced Dimerization for Chemo‐optogenetic Control of Protein and Organelle Positioning

Tunable and Photoswitchable Chemically Induced Dimerization for Chemo‐optogenetic Control of Protein and Organelle Positioning

The Life Science Toolbox Provided by Chemical Biology

A Photo‐responsive Small‐Molecule Approach for the Opto‐epigenetic Modulation of DNA Methylation

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