Photoinduced in situ generation of a DNA-binding benzothiazoloquinolinium derivative

Berdnikova, Daria V.; Федорова, О. А.; Gulakova, E. N.; Ihmels, Heiko

doi:10.1039/c2cc30958k

Cited by 29 publications

(18 citation statements)

References 31 publications

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“…We selected "dark" (all-E) and "lit" (360 nm, mostly-Z; or 420 nm, mixed E and Z) illumination conditions for further use in long-term cell culture. 42 Pleasingly for our design aims, reversible photoisomerisations with high-power illuminations repeatedly traversing the biologically applicable range 360 -420 nm showed no signs of causing photodegradation, under aerobic aqueous conditions (Fig 1d).…”

Section: Resultsmentioning

confidence: 88%

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

Gao

Kraus

Wranik

et al. 2019

Preprint

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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 ...

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Section: Resultsmentioning

confidence: 88%

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

Gao

Kraus

Wranik

et al. 2019

Preprint

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“…CBn based system [a] Medium [b] c Analyte (mM) [c] logK a [d] Detection method [e] Miscellaneous information [f ] Ref Cd 2 + CB7'BIBPA PB (10 mM, pH 6.5)~1 0 À3 4.92 FL, ABA l abs = 272 l em = 299 [46] Zn 2 + CB7'BIBPA PB (10 mM, pH 6.5)~1 0 À2 4.86 FL, ABA l abs = 272 l em = 299 [46] Hg 2 + CB7'SYPY water~50 n.a. binding enhancement by CB7~25 ABS, ABA l abs = 480 [47] CB7'COU-1 water (pH 2)~1 0 2 7.20 FL, ABA l abs = 455 l em = 480 [48] Pb 2 + Graphene + AuNP + CB7 water~10 À3 -SERS, IDA Raman shifts: 1377, 1419 cm À1 detection in mixture with other metals [49] [a] dye abbreviations: BIBPA -N-(2-benzimidazolylmethyl)-N,N-bis(2-pyridylmethyl)-amine, SYPY -(E)-4-(4-(1,4-dioxa-7,13-dithia-10azacyclopentadecan-10-yl)styryl)-1-methylpyridinium perchlorate, COU-1 -7-(diethylamino)-N-(1,3-dihydroxy-2-(hydroxymethyl) propan-2-yl)-2-oxo-2H-chromene-3-carboxamide, AuNP -Gold nanoparticles; for chemical structures of dyes, see 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 reduction reagents etc), which means that CBn-based chemosensors can potentially be utilised in a wide range of reaction media, e. g., for monitoring enzymatic reactions even at extreme pH, and that they tolerate a wide range of cofactors and co-reagents. Besides, CBn are also redox-inert, which allows for setting up redox-based sensing schemes for redoxactive analytes, where CBn can be used as an additive, see section "direct signal generation through exploitation of intrinsic analyte features".…”

Section: Analytementioning

confidence: 99%

“…[23] Self-assembled 1 : 1 complexes of CB7 and cation-binding dye molecules (e. g., BIBPA, SYPY or COU-1, see Table 6), which operate in the ABA signal generation mode, were shown to possess promising sensing properties for the detection of transition metal cations (Table 1). , [46,47,48] IDAbased sensing of cations is also possible (Table S1 in the Supporting Information) but is inherently limited by the lower affinity of CBn hosts for cations and the wide cross reactivity of such chemosensing ensembles).…”

Section: Signal Generation Through Associative Binding Assay (Aba)mentioning

confidence: 99%

Chemical Sensors Based on Cucurbit[n]uril Macrocycles

Sinn

Biedermann

2018

Israel Journal of Chemistry

147

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Cucurbit[n]urils (CBn) are glycoluril‐based macrocyclic hosts that bind many biologically, medicinally and environmentally relevant analytes with record high affinities in aqueous media. They are therefore prime candidates for the design of chemosensors that are operational in biological fluids, waste and drinking water and have promising potential to be utilized for in vitro and in vivo sensing and imaging applications. Unlike protein‐based antibodies, CBn can be prepared in multi kilogram scales, they are chemically robust and they show a desired fast analyte‐binding kinetics. Unlike protein‐based antibodies, CBn can be prepared in multi kilogram scales, are chemically robust and show a desired fast analyte‐binding kinetics Selective analyte detection and differentiation is possible owing to the charge‐ and size‐selective binding characteristics of the CBn members and due to the wide range of cyclic and acyclic CBn derivatives that differ in their analyte binding preference. Because CBn hosts are spectroscopically silent in the visible electromagnetic spectrum, optical signal transduction with CBn based chemosensing ensembles is typically performed by indicator displacement assays (IDA), which are easy to implement and applicable to both aliphatic and aromatic analytes. The extension to array‐based sensing with CBn chemosensors is straightforward. Associative binding assays (ABA), which are uniquely available with CB8‐based self‐assembled receptors offer superior analyte differentiation possibility due to emerging spectral fingerprints in the absorbance, circular dichroism (CD) and emission spectra for the receptor•analyte complexes. Direct signal generation is promising for inherently spectroscopically active analytes, for instance through absorbance, CD, emission and surface enhanced Raman spectroscopy (SERS). Sensitive NMR (19F, 129Xe) techniques, electron spin resonance (ESR), redox, and mass spectrometry are also valuable signal transduction options for specific analytes. CBn based chemosensors were successfully utilized for the monitoring of biophysical processes and enzymatic reactions with label free analytes or substrates in real time. These applications capitalize on the fast equilibration kinetics of CBn‐analyte complexes and the bio‐compatibility of CBn hosts. The tabulated large body of data extracted from reported CBn‐based binding studies is hoped to provide the reader with a valuable starting point for designing practically applicable CBn‐based sensors.

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“…Reversible control of DNA hybridization by external stimuli is essential for the realization of DNA‐based machines, DNA switches, dynamic and self‐assembled DNA materials and nanostructures, and drug delivery . Thus, small‐molecule ligands whose DNA‐binding properties can be modulated through photochemical reactions, redox reactions, prototropic equilibrium, metal ion coordination, or a combination of these, can be employed as “switchable” ligands to control the stability of double‐stranded DNA and, in selected cases, induce hybridization or denaturation of DNA strands . However, in the cited examples, the binding of ligands to double‐stranded DNA is not sequence‐specific.…”

Section: Figurementioning

confidence: 99%

Copper(II)‐Controlled Molecular Glue for Mismatched DNA

et al. 2017

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Isothermal hybridization of two DNA strands bearing three thymine-thymine (T:T) mismatches can be brought about in the presence of a stoichiometric amount of a bis-naphthalene macrocycle, 2,7-BisNP-NH. This process can be reverted by addition of a Cu salt due to formation of a dinuclear metal complex which does not bind to DNA. Subsequent sequestration of Cu releases the macrocycle and restores the hybridization state of DNA strands, thus allowing implementation of a fast fluorescent two-state DNA switch.

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Photoinduced in situ generation of a DNA-binding benzothiazoloquinolinium derivative

Cited by 29 publications

References 31 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

Chemical Sensors Based on Cucurbit[n]uril Macrocycles

Copper(II)‐Controlled Molecular Glue for Mismatched DNA

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