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Independent Research

39 F Coelho, S Saidjalolov, D Moreau, O Thorn-Seshold, S Matile*;

Inhibition of Cell Motility by Cell-Penetrating Dynamic Covalent Cascade Exchangers: Integrins Participate in Thiol-Mediated Uptake.
JACS Au 2023 ASAP (j5sn)

Thiol-mediated uptake: which are the proteins behind it? Until now, only the transferrin receptor (TfR) had been identified, but its expression & dynamics seem unlikely to provide much TMU. Following a hunch, we tested if the redox-regulatable poly(Cys) integrin proteins offer the extracellular polyCys, flexibility, and self-clustering to be major TMU tracks. And they are! We reveal that the TMU of thiol/disulfide cascade exchanger motifs (CAXs) known since a decade is greatly abolished just by knocking out the β1 integrin - an astonishing home run for a hypothesis-driven shot in the dark. We also show that these CAXs block integrin-dependent cell migration with potency correlating to their TMU activity. This paper builds the first links from reversible thiol-reactivity as a driving principle for nature's macromolecules to enrich interactions at the cell surface, across to how small molecule chemistry can harness or subvert it in subtle and useful ways. Stay redox-tuned!

38* L Zeisel#, J Felber#, K Scholzen, C Schmitt, A Wiegand, L Komissarov, E Arnér, O Thorn-Seshold*;

Bifunctional, piperazine-fused cyclic disulfides for oxidoreductase-activated cellular proagents.
ChemRxiv 2023 (

There remain no cellularly-effective reagent systems to selectively address dithiol reductases like Trxs and Grxs. Here, we developed piperazine-fused six-membered-cyclic disulfides that fill this gap, giving probes that are >100-fold faster activated than any previously known. These mildly strained diastereomeric bicycles are good substrates for glutaredoxins and thioredoxins, and the cis-disulfide series XS66 effectively reports oxidoreductase activity in the thioredoxin system in live cells. Late-stage diversifications can also apply these motifs not just for redox probes and prodrugs, but also for solid phase synthesis or in antibody-drug conjugates. This work thus establishes tuned dichalcogenides as effective, acute, bioreductive cellular triggers.

37* J Felber, A Kitowski, L Zeisel, M Maier, C Heise, J Thorn-Seshold, O Thorn-Seshold*;

Cyclic dichalcogenides extend the reach of bioreductive prodrugs to harness the thioredoxin system: applications to seco-duocarmycins.
ACS Central Science 2023 ASAP (j4cq)

Despite their crucial roles in physiology as well as links to cancer and inflammation, cellular dithiol-type oxidoreductases such as the Trx/TrxR system cannot be addressed by current bioreductive prodrugs, that mainly cluster around oxidised nitrogen species. Here we harnessed artificial dichalcogenides to gate the bioactivity of a series of 10 "off-to-on" reduction-activated cytotoxic duocarmycin prodrugs. Cell-free profiling and screening across 177 cell lines led us to quantify an index of reduction-specific activation, thanks to hydrolytic controls. Next, a combination of good tolerability with robust antitumour efficacy was shown in vivo in mouse models of breast and pancreatic cancer: a challenge with this famously toxic cargo. This work thus introduces tuned dichalcogenides as a platform strategy for specific bioreduction-based drug release from cell culture to in vivo.

36* L Zeisel*, M Maier, O Thorn-Seshold*;

Regioselective, efficient and scalable syntheses of 1,2-thiaselenanes.
Synthesis 2023, 1385-1393 (jxfb) (preprint, PDF)

1,2-thiaselenane-amines are valuable redox-active motifs for chemical biology, but their use is hindered by tedious synthesis. Here we develop their first regioselective syntheses, leveraging an aziridine intermediate and a kinetically controlled S-acylation for the regioselective chalcogen installations. Short, fast sequences with just 1-2 chromatographic steps cheaply deliver these motifs on scale for high-throughput inhibitor screening, and provide robust methods for other dichalcogenides.

35 C Velasco, R Santarella-Mellwig, M Schorb, L Gao, O Thorn-Seshold, A Llobet;

Microtubule depolymerization contributes to spontaneous neurotransmitter release.
Communications Biology 2023 ASAP (10.1038/s42003-023-04779-1)

Microtubule depolymerization contributes to spontaneous neurotransmitter release.

34* J Felber*, O Thorn-Seshold*;

40 Years of Duocarmycins: A Graphical Structure/Function Review of Their Chemical Evolution, from SAR to Prodrugs and ADCs.
JACS Au 2022, 2636–2644 (jmj2) ; correction
*Highlighted as the Editors' Choice article across the ACS for 15th Nov
A0 Poster: the Top 200 Duocarmycins

Duocarmycins are picomolar cytotoxins with fascinating, cyclisation-based bioactivity. We present an A0-size Poster "The Top 200 Duocarmycins", colour-coded by functional motifs, to narrate a structure-and-chronology overview of 600 research reports. The structures digitally hyperlink to their paper DOIs; or the vectorial poster can be printed to hang in hallways, for an accessible overview even without text. We concisely analyse their SAR, prodrugs, antibody-drug conjugates, and clinical trials, showing the duocarmycins as a platform with unique opportunities for rationally designed prodrugs and therapeutics.

33* M Müller, K Niemeyer, N Urban, N Ojha, F Zufall, T Leinders-Zufall, M Schaefer, O Thorn-Seshold*;

BTDAzo - a photoswitchable TRPC5 channel activator.
Angewandte Chemie 2022, 61, e202201565 (h2wb)

The TRPC5 calcium-permeable cation channel has distinct tissue-specific roles, from synaptic function to hormone regulation.
Here we develop the first photoswitchable TRPC5-activating reagent, BTDAzo, which can photocontrol TRPC5-based neuronal calcium responses from cell culture to mouse brain slices, for high-precision research in TRP channel biology. (BTDAzos are also the first azo-benzothiadiazines, an accessible and conveniently derivatised azoheteroarene with excellent two-colour photoswitching).

32* L Zeisel, J Felber, K Scholzen, L Poczka, D Cheff, M Maier, Q Cheng, M Shen, M Hall, E Arnér, J Thorn-Seshold, and O Thorn-Seshold*;

Selective cellular probes for mammalian thioredoxin reductase TrxR1:
rational design of RX1, a modular 1,2-thiaselenane redox probe.
Chem 2022, 1493-1517 (hq87) (preprint with Supp Info )

The answer is Selenium! The question: how to make small molecule probes that are selective cellular reporters of the unique selenol/thiol redox enzyme Thioredoxin Reductase (TrxR), an upstream driver in metabolism and disease?
We regiospecifically place a "dual-duty" selenium, to both (1) recruit the target selenol of TrxR, yet also (2) kinetically block monothiol reduction by futile cycling. We use the flipped regioisomer as a design control, highlighting the role of 5- vs 6-exo-trig cyclisation kinetics in avoiding reduction by non-target monothiols (with million-fold higher cellular concentrations than our target TrxR). By adding regioisomeric reactivity control to the dichalcogenide topology and geometry control we previously established, this paper delivers RX1: the first cellularly-selective bioreduction probe for mTrxR.

Lukas' Potential Energy highlight: 10.1016/j.chempr.2022.04.014 (gp4s84)
Highlights Hondal, Redox Biology 2022; Johansen-Leete & Payne, Chem 2022

31* L Gao, J Meiring, A Varady, I Ruider, C Heise, M Wranik, C Velasco, J Taylor, B Terni, J Standfuss, C Cabernard, A Llobet, M Steinmetz, A Bausch, M Distel, J Thorn-Seshold, A Akhmanova, and O Thorn-Seshold*;

In vivo photocontrol of microtubule dynamics and integrity, migration and mitosis, by the potent GFP-imaging-compatible photoswitchable reagents SBTubA4P and SBTub2M.
Journal of the American Chemical Society 2022, 5614-5628 (hk66)

General in vivo photopharmacology comes one step closer to reality!
Photopharmaceuticals in 2D cell culture can deliver target-selective potency with spatiotemporal specificity, through local illumination of globally-treated samples. But in 3D and in vivo, this has essentially not been reproduced. Here, we optimise a novel photoswitch for microtubule inhibition in vivo, ensuring it stays fully compatible with multiplexed fluorescent protein imaging. Its mechanism of action is reproducible from cell culture through to 3D systems (organoids, whole brain explant) through to classic animal models (zebrafish, clawed frog): systemic SBTub2M or SBTubA4P treatment plus spatiotemporally-localised illuminations photocontrol microtubule dynamics, MT network architecture, cell migration and cell division with cellular precision and second-level resolution in vivo. These in vivo-capable reagents can rewire how we aim for high-precision cytoskeleton research in cargo transport, cell motility, cell division and development. Their design will also be extended to a range of other protein targets.

30* J Felber, L Poczka, K Scholzen, L Zeisel, M Maier, S Busker, U Theisen, C Brandstädter, K Becker, E Arnér, J Thorn-Seshold, and O Thorn-Seshold*;

Cyclic 5-membered disulfides are not selective substrates of thioredoxin reductase, but are opened nonspecifically by thiols.
Nature Communications 2022, 13, 1754 (hn4h)

Cyclic five-membered disulfides (S50 dithiolanes) are kinetically labile motifs, that are widely used as "TRFS" redox probes for thioredoxin reductase (TrxR) e.g. in inhibitor screening and disease analysis. We show that the past decade's papers interpreting them as TrxR reporters may need retraction. Dithiolane probes are nonspecifically reduced by a range of thiols and proteins, are barely affected by TrxR inhibition or knockout, and even switch on spontaneously by polymerisation. We show why misinterpretations have arisen, and we present a robust approach to better orient future redox research.

29* L Gao, Y Kraus, A Stegner, T Wein, C Heise, L von Brunn, E Fajardo-Ruiz, J Thorn-Seshold, O Thorn-Seshold*;

Self-reporting styrylthiazolium photopharmaceuticals: mitochondrial localisation as well as SAR drive biological activity.
Org Biomol Chem 2022, 20, 7787-7794 (jjtb) (preprint )

Novel photoswitches are needed to drive advances in photopharmacology.
We present the first cellular trials of StyTz and StyBtz: E/Z-photoswitches that are near isosteres to azobenzenes, but have red-shifted π→π* bands, self-reporting fluorescence, Z→E relaxation on biological timescales, and decent solubility (charge). We tested StyTz and StyBtz designed for microtubule inhibition. Although they were light-specifically active, our studies excluded microtubules as a target. Using its self-reporting fluorescence, we assigned their light-dependent activity instead to mitochondrial photodisruption. StyTz/StyBtz may prove interesting photopharmaceutical scaffolds for mitochondrial targets, albeit not for cytosolic ones.

28* A Müller-Deku, O Thorn-Seshold*;

Exhaustive catalytic ortho-alkoxylation of azobenzenes: flexible access to functionally diverse yellow-light-responsive photoswitches.
Journal of Organic Chemistry 2022, 16526–16531 (js5z) (preprint )

Per-ortho-alkoxylated azobenzenes have attractive photoswitching and functional potential, but were a nightmare to synthesise systematically.
Here we developed the first method for per-ortho-alkoxylation of azobenzene photoswitches. This gives better E→Z and Z→E photoisomerisations and red-shifts photoresponses by >100 nm; but it also enables late-stage lipophilicity tuning, isotopic tracer preparation, or water solubility installation; and the M2F2 photoswitches we now access can also outperform 'gold standard' tetrafluoro- or tetrachloro- systems. Both the scaffolds and the method may thus broadly impact photopharmacology.

27* O Thorn-Seshold*;

Chapter 36: Photoswitchable Cytotoxins (pp 873-919)
in Molecular Photoswitches (Z Pianowski, Ed.); Wiley 2022 (h2wc)

Cytotoxins are drugs whose targets are so essential to biology that inhibiting them causes cell death. Photoswitchable analogues of these cytotoxins promise valuable applications, leveraging high-precision optical control for unique modulation studies of these essential biological targets. However, they face stricter challenges in design and validation than other classes of photopharmaceuticals. Developments in the last decade have targeted the cytoskeleton, structural and genomic integrity, and signaling; and principles for the creation and use of these reagents have been clarified. The stage is set for further applications of photoswitchable cytotoxins in the life sciences.

26* O Thorn-Seshold*, J Meiring;

Chapter 26: Photocontrolling Microtubule Dynamics with Photoswitchable Chemical Reagents (pp 403-430)
in Microtubules (H. Inaba, Ed.); Springer, 2022 (hsb2) (preprint)

A practical quick-start guide for biologists to use photoswitchable chemical reagents in cells.

Optically controlling microtubules in vivo has gone from dream to reality in less than a decade. A range of photoswitchable chemical MT inhibitors from our group now allow sub-second and micron-scale spatiotemporal resolution of inhibition over MT dynamics and MT-dependent processes. However, there were still no user guides for biologists to establish photopharmaceutical assays; and the principles for high-quality assay design and validation have not been codified even in the chemistry community. We present:

(i) the basics of photoswitching small molecules;
(ii) their special performance, requirements, and limitations;
(iii) assay validation and benchmarking workflows including troubleshooting;
(iv) the major photoswitchable MT inhibitors available;

(v) workflows to establish cellular assays optically controlling MT dynamics with temporal reversibility and spatial specificity down to a single selected cell.

These methods are generally translatable to establishing and benchmarking assays with photopharmaceuticals for any protein target; and should help chemists to develop photoswitchable reagents more robustly, as well as equipping biologists to apply them further to 3D culture and in vivo.

25. J Rushworth, et al., O Thorn-Seshold, M Fuchter*;
[5]-Helistatins: Tubulin binding helicenes with antimitotic activity.
JACS Au 2022, 2561–2570 (jhgf)
Helicenes are scaffolds with high synthetic and technological interest, that have not yet reached applications as cellular bioactives. We developed a first-in-class antimitotic helicene, helistatin, as a mimic of colchicine. Helistatin blocks MT polymerisation cell-free and in live cells. This demonstrates the feasibility of using helicenes as bioactive scaffolds, with potential as near-isosteres of biaryls or cis-stilbenes.

24. M Scheck, et al., G Barba-Spaeth, O Thorn-Seshold, A Krug, S Endres, S Rothenfusser*, J Thorn-Seshold*; FluoRNT: A robust, efficient assay for the detection of neutralising antibodies against yellow fever virus 17D.
PLoS One 2022, 17, e0262149 (hgjw)
There is an urgent need for high-throughput, scalable, rapid, cheap and robust methods to quantify patient protective antibody titres against viral infection. We develop FluoRNT, a flow cytometry method using a fluorescent viral variant of yellow fever, that is 10-100-fold more efficient than current methods, fully automatisable, and minimises time of contact with patient samples. The assay system ensures significantly greater data precision and reproducibility than current methods, enabling sensitive quantitative studies.

23. F Küllmer, N Vepřek, et al., O Thorn-Seshold, H-D Arndt, D Trauner; Next Generation Opto-Jasplakinolides Enable Local Remodeling of Actin Networks.
Angewandte Chemie 2022, e202210220 (jbcz) (preprint )
We introduce 2nd generation photoswitchable actin inhibitors, neoOptoJasps, based on insights from CryoEM and SAR studies. They can be photoactivated with blue light, then relax spontaneously and rapidly to their less active isomer. They enable reversible control of F-actin dynamics and migration in live cells; and sub-cellular photoactivation in peripheral regions locally influences cytoskeleton stability and dynamics. These tools will empower spatiotemporally precise studies of the actin cytoskeleton.

22. M Ober, A Müller-Deku, et al., O Thorn-Seshold, B Nickel;
SAXS measurements of azobenzene lipid vesicles reveal buffer-dependent photoswitching and quantitative Z→E isomerisation by X-rays.
Nanophotonics 2022, 11, 2361-2368 (h2v6)
We study the switching of photoresponsive lipid membranes with small-angle X-ray scattering, showing that soft X-rays can quantitatively isomerise photolipid membranes to the all-trans state: both enabling more powerful X-ray-based membrane control and underlining the role of high energy X-rays for observation-only soft matter experiments.

21* L Gao, J Meiring, C Heise, A Rai, A Müller-Deku, A Akhmanova, J Thorn-Seshold, and O Thorn-Seshold*;

Photoswitchable epothilone-based microtubule stabilisers allow GFP-imaging-compatible, optical control over the microtubule cytoskeleton.
Angewandte Chemie VIP paper 2021, 61, e202114614 (g94z)

Epothilone and Taxol, C=C photoswitches new and old: here, we bring the GFP-orthogonal azobenzene isostere styrylthiazole (ST) into photopharmacology. The nanomolar-potent STEpo reagents are photoswitchably microtubule-stabilising reagents with micron-precise targeting and intriguing potential towards in vivo applications.

20* A Sailer, J Meiring, C Heise, L Pettersson, A Akhmanova, J Thorn-Seshold, and O Thorn-Seshold*;

Pyrrole hemithioindigo antimitotics with near-quantitative bidirectional photoswitching photocontrol cellular microtubule dynamics with single-cell precision.
Angewandte Chemie 2021, 60, 23695-23704 (gs63) , SynFacts

Most photopharmaceuticals suffer background activity, as their photoswitching is incomplete. Our PHTubs are near-quantitatively-switchable reagents that deliver cell-precise real-time photocontrol over microtubule dynamics, cell cycle, and cell death, for high-precision cytoskeleton research. This is the first use of hemithioindigos for high-resolution control in live cell assays, and shows PHTs may be excellent scaffolds for a range of other biological targets.

19* J Felber, L Zeisel, L Poczka, K Scholzen, S Busker, M Maier, U Theisen, C Brandstädter, K Becker, E Arnér, J Thorn-Seshold, and O Thorn-Seshold*;

Selective, modular probes for thioredoxins enabled by rational tuning of a unique disulfide structure motif.
Journal of the American Chemical Society 2021, 143, 8791–8803 (gkbxdd)

Cyclic disulfides have a lot of potential for redox biology! Here we rationally design unique S6x disulfides, invoking a combination of considerations for topology, thermodynamics, and kinetics. These give the only disulfide-based probes that can resist the cellular monothiol background; and they proved to be selectively triggered by the central redox effector protein, thioredoxin (Trx). The methodology in this paper forms the basis for our longterm project on redox biology.

18* L Gao, J Meiring, Y Kraus, M Wranik, T Weinert, S Pritzl, R Bingham, E Ntouliou, K Jansen, N Olieric, J Standfüss, L Kapitein, T Lohmüller, J Ahlfeld, A Akhmanova, M Steinmetz, and O Thorn-Seshold*;

A robust, GFP-orthogonal photoswitchable inhibitor scaffold extends optical control over the microtubule cytoskeleton.
Cell Chemical Biology 2021, 28, 228-241 (f5qh); SynFacts (preprint )

It's no use photoswitching if you can't see what you're doing, or if the switch falls apart while you use it. These heterostilbene SBTubs were developed to leave GFP/YFP imaging channels free, and also resist in vivo metabolism. They allow exquisitely orthogonal photocontrol of cellular microtubule dynamics with minimal crosstalk/bleaching.

17* O Thorn-Seshold*, J Felber, J Thorn-Seshold, L Zeisel;

Disulfide prodrug compounds.
Patent WO 2022/200347 (EP21163944.8), 2021.

A modular probe & prodrug system using disulfide redox chemistry.

16* O Thorn-Seshold*, L Zeisel, J Felber;

Dichalcogenide Prodrugs.
Patent WO 2022/214598 (EP21167187.0), 2021.

A modular probe & prodrug system using dichalcogenide redox chemistry.

15* A Müller-Deku, J Meiring, K Loy, Y Kraus, C Heise, R Bingham, K Jansen, X Qu, F Bartolini, L Kapitein, A Akhmanova, J Ahlfeld, D Trauner, O Thorn-Seshold*;

Photoswitchable paclitaxel-based microtubule stabilisers allow optical control over the microtubule cytoskeleton.
Nature Communications 2020, 11, 4640 (gnsd)

These AzTax reagents (azobenzene-extended taxols) are the first photoswitchable microtubule stabilisers. They enable cellularly- and subcellularly-specific photocontrol of MT polymerisation dynamics, incl. in primary neurons.

14* Y Kraus#, C Glas#, B Melzer, L Gao, C Heise, M Preuße, J Ahlfeld, F Bracher, O Thorn-Seshold*;

Isoquinoline-based biaryls as a robust scaffold for microtubule inhibitors.
European Journal of Medicinal Chemistry 2020, 111865 (h2wd) (preprint )

Colchicinoids have two aryl blades separated by a bridge that is often metabolically or photochemically labile. These IQTub biaryls are highly robust; easy to make and diversify; and are potent druglike cellular binders.

13* A Sailer, F Ermer, Y Kraus, R Bingham, F Lutter, J Ahlfeld and O Thorn-Seshold*;

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo.
Beilstein Journal of Organic Chemistry 2020, 125 (hkx8)

Improving on our first generation photoswitchable microtubule inhibitor HTIs, these HITubs are mid-nanomolar cell-active photoswitchable tubulin binders with all-visible-light switching, illustrating the potential of the HTI scaffold for cell biology.

12. U Theisen, A Ernst, R Heyne, T Ring, O Thorn-Seshold, R Köster; Microtubules and motor proteins support zebrafish neuronal migration by directing cargo.
Journal of Cell Biology 2020, 219, e201908040 (h2v7).
Not only motile cell types but also neurons require dynamic MTs during motion. Spatiotemporally precise inhibition of their MTs with PST-1 links MT-based protein relocalisation to migration speed and directionality.

11. M Borowiak, F Küllmer, F Gegenfurtner, S Peil, V Nasufovic, S Zahler, O Thorn-Seshold, D Trauner, H-D Arndt; Optical manipulation of F-actin with photoswitchable small molecules.
Journal of the American Chemical Society 2020, 142, 9240 (gzht).
These OptoJasps (azobenzene-extended jasplakinolides) are the first photoswitchable inhibitors for actin dynamics. They enable cellularly-targeted modulation of cell motility and other actin-dependent processes.

10. A Kopf, J Renkawitz, R Hauschild, I Girkontaite, K Tedford, J Merrin, O Thorn-Seshold, D Trauner, H Häcker, K-D Fischer, E Kiermaier and M Sixt; Microtubules control cellular shape and coherence in amoeboid migrating cells.
Journal of Cell Biology 2020, 219, e201907154 (ggzn8n) (preprint )
Using PSTs to spatiotemporally precisely inhibit MT dynamics in highly motile cells revealed the roles of MTs in maintaining cell shape and coordinating retractions with actomyosin.

9. M Bischof, S Olthoff, C Glas, O Thorn-Seshold, M Schaefer, K Hill; TRPV3 endogenously expressed in murine colonic epithelial cells is inhibited by the novel TRPV3 blocker 26E01.
Cell Calcium 2020, 92, 102320 (h2v8).
26E01 was identified as a nontoxic blocker of TRPV3 currents in overexpression and native-expression cellular systems, that does not affect TRPV1, TRPV2, and TRPV4 channels.

8* O Thorn-Seshold*;

Comment on “Photo-Controlled Reversible Microtubule Assembly”.
Angewandte Chemie 2020, 59, 7652-7654 (h2wf)

Metabolically labile inhibitor-photoswitch attachment strategies and PAINS-like aggregation modulation can confound reagent design. This critique to Liu et al., ACIE 2018 highlights the danger of neglecting controls and SAR. Despite their followup showing that non-inhibitory analogues give identical effects (Liu et al., ACIE 2019) the initial paper is still not retracted (author response here).

7* A Sailer, F Ermer, Y Kraus, F Lutter, C Donau, M Bremerich, J Ahlfeld and O Thorn-Seshold*;

Hemithioindigos for cellular photopharmacology: desymmetrised molecular switch scaffolds enabling design control over the isomer-dependency of potent antimitotic bioactivity.
ChemBioChem 2019, 1305-1314 (hb5v)

The understudied hemithioindigos have more attractive photoswitching than standard azobenzenes. These HOTubs are the first HTI-pharmacophore reagents to succeed in cell biology, and enable desymmetrised designs.

6* O Thorn-Seshold*, F. Bracher, B. Melzer;

Isoquinoline biaryl compounds.
Patent EP18207030, 2018.

IQTubs are diversifiable, metabolically robust isosteres for cis-stilbenoid bioactives.

5. A Singh, T Saha, I Begemann, A Ricker, H Nüsse, O Thorn-Seshold, J Klingauf, M Galic, M Matis; Polarized microtubule dynamics directs cell mechanics and coordinates forces during epithelial morphogenesis.
Nature Cell Biology 2018, 20, 1126 (gfcc9p).
Spatiotemporally resolved, reversible PST photoswitching elucidates the need for dynamic MTs in force generation to orient drosophila tissue development.

4. J Zenker, MD White, RM Templin, RG Parton, O Thorn-Seshold, S Bissiere, N Plachta; A microtubule-organizing center directing intracellular transport in the early mouse embryo.
Science 2017, 357, 925 (gbwmgk).
Spatiotemporally resolved, reversible PST photoswitching elucidates the location and origin of the non-centrosomal MT-organising system in the early stages of mammalian development.

3. K Eguchi, Z Taoufiq, O Thorn-Seshold, et al., T Takahashi; Wild-type monomeric α-synuclein can impair vesicle endocytosis and synaptic fidelity via tubulin polymerization at the calyx of Held.
The Journal of Neuroscience 2017, 37, 6043 (gbjstw).
Temporally reversible MT inhibition applied using PST photoswitching contributes to understanding vesicle trafficking dynamics in neurons.

2* M Borowiak, et al., D Trauner*, O Thorn-Seshold*;

Photoswitchable Inhibitors of Microtubule Dynamics Optically Control Mitosis and Cell Death.
Cell 2015, 162, 403-411 (f7kcps)

Reversible photoswitching of PSTs allows bidirectionally reversible optical modulation of MT dynamics in live cells, and modifies cell division sequences during embryonic development.

1* O Thorn-Seshold*, M Borowiak, D Trauner, J Hasserodt;

Azoaryls as Reversibly Modulatable Tubulin Inhibitors.
Patent WO2015166295, 2014.

Reversibly photoswitchable isosteres of stilbenoid colchicine-mimic drugs ("PSTs") for in vitro and in vivo control of microtubule dynamics.

Studies & PhD

O Thorn-Seshold, M Vargas-Sanchez, S McKeon, J Hasserodt; A Robust, High-Sensitivity Stealth Probe for Peptidases. Chem. Comm. 2012, 48, 6253-6255.

J Hasserodt, O Thorn-Seshold; Fluorogenic Peptidase Substrate. Patent WO2013045854, 2011.

D Konkolewicz, O Thorn-Seshold and A Gray-Weale; Models for randomly hyperbranched polymers: Theory and simulation. J. Chem. Phys. 2008, 129, 054901.

MM Bishop, LF Lindoy, M McPartlin, A Parkin, O Thorn-Seshold, P Turner; A systematic study of ligand intermolecular interactions in crystals of copper(II) complexes of bidentate guanidino derivatives. Polyhedron 2007, 26, (2), 415-429.

MM Bishop, SJ Coles, A Lee, LF Lindoy, A Parkin, O Thorn-Seshold, P Turner; A Structural Study of Tautomerism and Hydrogen-Bonding in Supramolecular Assemblies. Supramol. Chem. 2005, 17, (7), 567-578.

MM Bishop, LF Lindoy, O Thorn-Seshold, RO Piltz, P Turner; A Supramolecular Assembly Containing an Unusually Short N-H∙∙∙N Hydrogen Bond. J. Het. Chem. 2001, 38, (6), 1377-1382.