Optical control of sphingosine-1-phosphate formation and function

Morstein, Johannes; Hill, Rose Z.; Novák, A.; Feng, Suihan; Norman, Dean C.; Donthamsetti, Prashant; Frank, James A.; Harayama, Takeshi; Williams, Benjamin M.; Parrill, Abby L.; Tigyi, Gábor; Riezman, Howard; Isacoff, Ehud Y.; Bautista, Diana M.; Trauner, Dirk

doi:10.1038/s41589-019-0269-7

Cited by 81 publications

(75 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Particularly in the context of in vivo microtubule research it should be pointed out that CA4-like MT inhibitors (which SBTubs mimic) are most often applied as vascular disrupting agents and studied using surface-illumination imaging by one-and two-photon microscopy 57 -which we here demonstrate are feasible approaches to photoswitch the SBT scaffold. In these superficial tissue settings, the penetration of violet light required for SBTub isomerisation is not problematic; our ongoing results as well as published reports 58 have shown successful subcutaneous isomerisation of photoswitches even with simple transdermal 360 nm LED illumination. Rather than light accessibility for tissues, we consider that two compound-specific factors are likely to determine the success of reaching in vivo applications with in situ-actuated photoswitches for intracellular targets.…”

Section: Discussion and Outlookmentioning

confidence: 55%

Photoswitchable microtubule inhibitors enabling robust, GFP-orthogonal optical control over the tubulin cytoskeleton

Gao

Kraus

Wranik

et al. 2019

Preprint

View full text Add to dashboard Cite

Here we present GFP-orthogonal optically controlled reagents for reliable and repetitive in cellulo modulation of microtubule dynamics and its dependent processes. Optically controlled reagents ("photopharmaceuticals") have developed into powerful tools for high-spatiotemporal-precision control of endogenous biology, with numerous applications in neuroscience, embryology, and cytoskeleton research. However, the restricted chemical domain of photopharmaceutical scaffolds has constrained their properties and range of applications. Styrylbenzothiazoles are an as-yet unexplored scaffold for photopharmaceuticals, which we now rationally design to feature potent photocontrol, switching microtubule cytoskeleton function off and on according to illumination conditions. We show more broadly that this scaffold is exceptionally chemically and biochemically robust as well as substituent-tolerant, and offers particular advantages for intracellular biology through a range of desirable photopharmaceutical and drug-like properties not accessible to the current classes of photoswitches. We expect that these reagents will find powerful applications enabling robust, high precision, optically controlled cell biological experimentation in cytoskeleton research and beyond. Introduction:Molecular photoswitches have been used to install optical control over a broad range of phenomena, with applications from material sciences 1,2 through to reversible photocontrol of ligand binding affinities 3 and manipulation of diverse cellular processes in chemical biology 4,5 . For studies of temporally-regulated and spatially anisotropic biological systems, particularly those that simultaneously support several cellular functions, photoswitchable inhibitors conceptually enable a range of powerful studies not accessible with other tool systems. [6][7][8] A prime example of such spatiotemporally regulated, multifunctional systems is the microtubule (MT) cytoskeleton. This complex cellular network plays central roles in nearly all directed mechanical processes, such as intracellular transport and cell motility; its crucial function in cell proliferation has also made it a central anticancer drug target. 9-11 Yet, whereas cytoskeleton research typically aims to study a subset of MT-dependent processes that are spatially and/or temporally localised, nearly all MT inhibitors reported as tool compounds for biological research are drugs that are active wherever they are distributed, including at sites and at times where drug activity is not desired. 12 This restricts the scope of applications and utility of these inhibitors for selective research into the various, highly dynamic, anisotropic processes dependent on MTs. 13 The structure of the colchicine site MT inhibitor combretastatin A-4 (CA4; Fig 1a) 14 has recently inspired photoswitchable solutions to the problem of achieving spatiotemporal control over MT inhibition. CA4 is a stilbene whose Z-isomer (cis) binds tubulin, acts as a low nanomolar cytotoxin in cellulo, and reached Phase III trials as an ...

show abstract

Section: Discussion and Outlookmentioning

confidence: 55%

Photoswitchable microtubule inhibitors enabling robust, GFP-orthogonal optical control over the tubulin cytoskeleton

Gao

Kraus

Wranik

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Freely diffusible azobenzene photoswitches that are active in their trans-form have been developed for av ariety of targets.T hese include GPCRs,s uch as the m-opioid receptor, [17] the M1 muscarinic receptor, [54] the sphingosine phosphate receptor S1PR1, [55] and the metabotropic glutamate receptor mGluR5, [18] and ion channels,s uch as GA-BAA, [56,57] a7n AChR, [14] and ionotropic glutamate receptors. [15,37,58] Dark active photopharmaceuticals have also been used to optically control transporters,such as GAT1, [21] EAAT1-3, [22,23] and F 1 F 0 -ATPase, [59] as well as enzymes.…”

Section: Resultsmentioning

confidence: 99%

Sign Inversion in Photopharmacology: Incorporation of Cyclic Azobenzenes in Photoswitchable Potassium Channel Blockers and Openers

et al. 2019

Self Cite

View full text Add to dashboard Cite

Photopharmacology relies on ligands that change their pharmacodynamics upon photoisomerization. Many of these ligands are azobenzenes that are thermodynamically more stable in their elongated trans‐configuration. Often, they are biologically active in this form and lose activity upon irradiation and photoisomerization to their cis‐isomer. Recently, cyclic azobenzenes, so‐called diazocines, have emerged, which are thermodynamically more stable in their bent cis‐form. Incorporation of these switches into a variety of photopharmaceuticals could convert dark‐active ligands into dark‐inactive ligands, which is preferred in most biological applications. This “pharmacological sign‐inversion” is demonstrated for a photochromic blocker of voltage‐gated potassium channels, termed CAL, and a photochromic opener of G protein‐coupled inwardly rectifying potassium (GIRK) channels, termed CLOGO.

show abstract

Section: Resultsmentioning

confidence: 99%

Sign Inversion in Photopharmacology: Incorporation of Cyclic Azobenzenes in Photoswitchable Potassium Channel Blockers and Openers

Trads¹,

Hüll²,

Matsuura³

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Photopharmacology relies on ligands that change their pharmacodynamics upon photoisomerization. Many of these ligands are azobenzenes that are thermodynamically more stable in their elongated trans-configuration. Often, they are biologically active in this form and lose activity upon irradiation and photoisomerization to their cis-isomer.Recently, cyclic azobenzenes,so-called diazocines,have emerged, which are thermodynamically more stable in their bent cis-form. Incorporation of these switches into av ariety of photopharmaceuticals could convert dark-active ligands into darkinactive ligands,w hichi sp referred in most biological applications.T his "pharmacological sign-inversion" is demonstrated for aphotochromic blocker of voltage-gated potassium channels,t ermed CAL, and ap hotochromic opener of G protein-coupled inwardly rectifying potassium (GIRK) channels,termed CLOGO.

show abstract

Optical control of sphingosine-1-phosphate formation and function

Cited by 81 publications

References 55 publications

Photoswitchable microtubule inhibitors enabling robust, GFP-orthogonal optical control over the tubulin cytoskeleton

Photoswitchable microtubule inhibitors enabling robust, GFP-orthogonal optical control over the tubulin cytoskeleton

Sign Inversion in Photopharmacology: Incorporation of Cyclic Azobenzenes in Photoswitchable Potassium Channel Blockers and Openers

Sign Inversion in Photopharmacology: Incorporation of Cyclic Azobenzenes in Photoswitchable Potassium Channel Blockers and Openers

Contact Info

Product

Resources

About