Light-cleavable rapamycin dimer as an optical trigger for protein dimerization

Brown, Kalyn; Zou, Yan; Shirvanyants, David; Zhang, Jie; Samanta, Subhas; Mantravadi, Pavan K.; Dokholyan, Nikolay V.; Deiters, Alexander

doi:10.1039/c4cc09442e

Cited by 45 publications

(47 citation statements)

References 47 publications

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“…[12] Computational and experimental studies confirmed that the formation of a FKBP– 4 –FKBP homodimer sterically blocked binding of FRB. Since 4 does not require the use of an engineered iFKBP or the use of an exogenous protein, such as avidin, this represents a more practical engineering approach for light-triggered dimerization.…”

Section: Optical Control Of Small Moleculesmentioning

confidence: 99%

“…In order to alleviate the need for an external avidin protein while still capitalizing on the dramatic steric demand provided through recruitment of ap rotein to the caging group,asecond rapamycin molecule was linked to generate the symmetric dimer 4 (Figure 3a). [12] Computational and a) The structure of 1 is shown with the caging group in red. In this system, FAK activity was monitored in the presence of 1 with and without UV exposure.…”

Section: Optical Activation Of Rapamycin-induced Protein Dimerizationmentioning

confidence: 99%

“…However,a fter UV irradiation and dimerization of split TEV,aluciferase reporter is proteolytically cleaved and luminescence is generated.A dapted with permission from Ref. [12].C opyright 2015 Royal Society of Chemistry.…”

Section: Optical Activation Of Other Chemical Inducers Of Protein Dimmentioning

confidence: 99%

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Optochemical Control of Biological Processes in Cells and Animals

et al. 2018

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Biological processes are naturally regulated with high spatial and temporal control, as is perhaps most evident in metazoan embryogenesis. Chemical tools have been extensively utilized in cell and developmental biology to investigate cellular processes, and conditional control methods have expanded applications of these technologies toward resolving complex biological questions. Light represents an excellent external trigger since it can be controlled with very high spatial and temporal precision. To this end, several optically regulated tools have been developed and applied to living systems. In this review we discuss recent developments of optochemical tools, including small molecules, peptides, proteins, and nucleic acids that can be irreversibly or reversibly controlled through light irradiation, with a focus on applications in cells and animals.

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Section: Optical Control Of Small Moleculesmentioning

confidence: 99%

Section: Optical Activation Of Rapamycin-induced Protein Dimerizationmentioning

confidence: 99%

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Optochemical Control of Biological Processes in Cells and Animals

et al. 2018

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“…Photoprotection of dopamine, 17 histidine, 17 GABA 18 , 19 and Vemurafenib 20 has been reported. Photoprotecting groups can also be used for controlling complex biological processes, like protein dimerization 21 or gene activation 22 and gene silencing. 23 …”

Section: Introductionmentioning

confidence: 99%

Green-Light-Sensitive BODIPY Photoprotecting Groups for Amines

2018

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We describe a series of easily accessible, visible-light-sensitive (λ > 500 nm) BODIPY (boron-dipyrromethene)-based photoprotecting groups (PPGs) for primary and secondary amines, based on a carbamate linker. The caged compounds are stable under aqueous conditions for 24 h and can be efficiently uncaged in vitro with visible light (λ = 530 nm). These properties allow efficient photodeprotection of amines, rendering these novel PPGs potentially suitable for various applications, including the delivery of caged drugs and their remote activation.

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“…Several light-inducible methods based on CIP have been reported using CIP inducers caged with different photosensitive groups. These caged CIP inducers (including ABA, rapamycin, gibberellic acid, and other synthetic dimerizers) [77,[97][98][99][100][101][102][103][104][105][106][107][108] were inactive for dimerization in the caged form but can be uncaged to regenerate active inducer upon light irradiation. This photo-controlled version of CIP should be readily adaptable for light inducible epigenome editing.…”

Section: Light Inducible Epigenome Editingmentioning

confidence: 99%

Chemical and Light Inducible Epigenome Editing

Zhao

Wang

Liang

2020

IJMS

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The epigenome defines the unique gene expression patterns and resulting cellular behaviors in different cell types. Epigenome dysregulation has been directly linked to various human diseases. Epigenome editing enabling genome locus-specific targeting of epigenome modifiers to directly alter specific local epigenome modifications offers a revolutionary tool for mechanistic studies in epigenome regulation as well as the development of novel epigenome therapies. Inducible and reversible epigenome editing provides unique temporal control critical for understanding the dynamics and kinetics of epigenome regulation. This review summarizes the progress in the development of spatiotemporal-specific tools using small molecules or light as inducers to achieve the conditional control of epigenome editing and their applications in epigenetic research.

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Light-cleavable rapamycin dimer as an optical trigger for protein dimerization

Cited by 45 publications

References 47 publications

Optochemical Control of Biological Processes in Cells and Animals

Optochemical Control of Biological Processes in Cells and Animals

Green-Light-Sensitive BODIPY Photoprotecting Groups for Amines

Chemical and Light Inducible Epigenome Editing

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