Tom Fiala

ChemiCator Welcome to ChemiCator! 🔬 Dive Deep into the Fascinating World of Organic Chemistry 🔬 Are you passionate about organic chemistry? Whether you're a student striving for excellence, a curious mind eager...

I believe communicating science and sparking interest in others is as important as doing the actual research. If you love organic chemistry, check out the Chemicator channel on Youtube! Beautiful graphics and nice explainers from an enthusiastic student.
www.youtube.com/@Chemicator

Mass spectrometry and enzyme assays refute histone tyrosine sulfation - Nature Chemical Biology Nature Chemical Biology - Mass spectrometry and enzyme assays refute histone tyrosine sulfation

TWeeP (This Week's Paper): The PTM sulfotyrosine is very hard to reliably identify due to instability and similarity to phosphoTyr. This week, I highlight a vivid debate in @natchembio.nature.com about the existence of sTyr in histones:
www.nature.com/articles/s41...
www.nature.com/articles/s41...

⭐🎉 Přinášíme skvělou zprávu a další obrovský úspěch! Tomáš Fiala, držitel Start-up grantu Nadace Experientia, získal prestižní ERC Starting grant pro mladé vědce! Svoji výzkumnou skupinu založí v říjnu 2025 na @masarykuniversity.bsky.social.

Tomášovi k tomuto úspěchu srdečně gratulujeme! 👏

The ERC awards €761m to the next generation of scientists in Europe The European Research Council (ERC) has selected 478 early-career researchers across Europe to receive this year’s Starting Grants. With a total funding of €761 million, these grants support excellent...

Grant alert! 🚨 I am honored to receive the @erc.europa.eu Starting Grant. In the PROTEOFORMER project, we will develop chemical tools for precise control of individual protein states, aiming to probe the origins of neurodegeneration. 🧪 Stay tuned!
#ERCStG erc.europa.eu/news-events/...

Immobilized acyl-transfer molecular reactors enable the solid-phase synthesis of sterically hindered peptides - Nature Chemistry Current solid-phase peptide synthesis methods struggle to incorporate sterically hindered amino acids. Now researchers have developed a ribosome-mimicking molecular reactor that bypasses two-phase acy...

TWeeP (This Week's Paper): Bulky amino acids are difficult to incorporate into peptides by SPPS. How about helping them out with induced proximity? Wei et al. do exactly that with their ribosome-inspired acyl-transfer linkers. Check them out in @natchem.nature.com!
www.nature.com/articles/s41...

A Functional Assay for Mining Noninhibitory Enzyme Ligands from One Bead One Compound Libraries: Application to E3 Ubiquitin Ligases Chemical dimerizers are synthetic molecules that bring into proximity two or more proteins that do not normally interact with one another. A major application of this technology is to recruit an enzym...

TWeeP (This Week's Paper): PROTACs and other chemical dimerizers are based on non-inhibitory ligands which are hard to come by. The Kodadek lab presents a clever assay for mining such binders using one bead–one compound libraries. Now out in @jacs.acspublications.org!
pubs.acs.org/doi/10.1021/...

London Dispersion as a Design Element in Molecular Catalysis This Perspective describes the role of London dispersion (LD) interactions as a key factor controlling chemical selectivity. LD arises from the correlated motion of electrons, leading to subtle yet significant stabilization (“steric attraction”), and counterbalances, together with other noncovalent interactions, Pauli exchange repulsion (“steric hindrance”). While chemists have largely relied on the latter to rationalize selectivities in catalyzed reactions, we emphasize here the role LD plays as a key design element in chemical reactions, in particular, for catalyst development.

TWeeP (This Week's Paper): As a fan of looking at (bio)organic reactions from a physico-chemical perspective, I like the perspective by Schreiner and coworkers on the role of London dispersion forces in catalytic reactions. Check it out now in @jacs.acspublications.org!
pubs.acs.org/doi/10.1021/...

TWeeP (This Week's Paper): Hemes are ubiquitous in nature. Yet, their trafficking and dynamics remain underexplored. That's about to change thanks to probes that label neighboring proteins upon activation by heme from Hirayama and coworkers in @jacs.acspublications.org!
pubs.acs.org/doi/full/10....

TWeeP (This Week's Paper): another fantastic publication from the Kanai lab in @jacs.acspublications.org. Check out how to generate isocyanates on demand from a stable hydroxamic acid–pyrrolidine conjugate and sulfonyl fluoride for fast protein labeling in live cells!
pubs.acs.org/doi/10.1021/...

We have multiple PhD and Postdoc positions open in my new group at Masaryk University. Are you an excellent and motivated candidate interested in organic and peptide synthesis and chemical biology? Get in touch! Start in January 2026. www.fialalab.com
Appreciate sharing!

TWeeP (This Week's Paper): Cool supramolecular chemistry of bambusuril macrocycles! In @chemcomm.rsc.org, Heck et al. show strong complexation of the astatide-211 anion. The complex is stable in human serum! Nice progress towards At-based radiopharmaceuticals.
pubs.rsc.org/en/Content/A...

Introduction of Reactive Thiol Handles into Tyrosine-Tagged Proteins through Enzymatic Oxidative Coupling Site-specific protein bioconjugation methods have enabled the development of new therapeutics and materials, and further development of existing techniques has expanded the compatible library of prote...

TWeeP (This Week's Paper): Introducing functional handles to proteins is crucial throughout chemical biology. In JACS (@pubs.acs.org), the Francis group use megaTYR, a bacterial tyrosinase, to modify Tyr residues with DTT, thus inserting exposed thiols to the target.
pubs.acs.org/doi/10.1021/...

Nadace Experientia zná držitele start-up grantu pro rok 2025!

👨‍🔬 Tomáš Fiala, který aktuálně působí na ETH Zürich, založí svoji výzkumnou skupinu na Masarykově univerzitě v Brně, kterou od ledna 2026 podpoří start-up grant Nadace Experientia ve výši 6 000 000 Kč.

Moc gratulujeme!

Visualization and Quantification of Base-Level SO2 in Live Cells without Intracellular Background Interference Using Sensitive 19F-NMR Sulfur dioxide (SO2), as an endogenous gasotransmitter, is involved in a variety of physiological processes in living systems, however, distinction and quantification of base-level SO2 in live cells p...

TWeeP (This Week's Paper): Visualizing sulfite in live cells with zero background? No problem with the sulfite-responsive 19F-NMR probe by Su and coworkers. Now out in JACS (@pubs.acs.org)!
pubs.acs.org/doi/full/10....

Selectively assembling collagen heterotrimers is a challenge. But not for us! Aminopropline-aspartate salt bridges drive the assembly of a hyperstable, a minimal-length, and a special blunt-ended collagen heterotrimer. Now out in
@angewandtechemie.bsky.social!
onlinelibrary.wiley.com/doi/10.1002/...

Water and Collagen: A Mystery Yet to Unfold Collagen is the most abundant protein in the human body and plays an essential role in determining the mechanical properties of the tissues. Both as a monomeric protein and in fibrous assemblies, coll...

TWeeP (This Week's Paper): A very nice review on the role of water in collagen structure and folding has been published in Biomacromolecules by Giubertoni and coworkers. Check it out!
pubs.acs.org/doi/full/10....

Hyperstable and Fibril-Forming Collagen-Mimetic Peptides in Shortest Triple Helices: Empowering the Capping by π-systems Developing collagen-mimetic peptides (CMPs) with short triple helices and fibril-forming ability remains challenging. Herein, we stabilized short CMPs (3–6 GPO repeats) by attaching extended aromatic π-system─fluorenyl groups at the N-terminus and tyrosine at the C-terminus. These modifications promoted triple helix folding through π–π interactions, acting as a “glue” to stabilize the structure and facilitate fibrillation. A single fluorenyl cap required 5 GPO repeats for helix formation, while double fluorenyl capping reduced this to 4 repeats. Notably, at pH 5.5, triple helices formed with only 3 GPO repeats. The double-capped CMPs exhibited hyperstability (Tm = 76 °C) and formed fibrillar networks at physiological pH. Biophysical and computational studies confirmed the role of π–π and CH–π interactions, along with hydrogen bonding, in stabilization. The minimalistic CMPs supported cell viability, demonstrating their potential for biomedical applications. This strategy offers a method to design highly stable, short CMPs that form robust fibrillar networks.

TWeeP (This Week's Paper): In Biomacromolecules, Mukherjee et al. present a neat way of stabilizing collagen triple helices and inducing their fibrillation via terminal aromatic capping groups. (Plus check out the fun TOC graphic!!)
pubs.acs.org/doi/abs/10.1...

This Norwegian biotech is developing next-gen fibrosis treatments Tribune Therapeutics raises $40 million to target the signaling pathways that drive fibrosis

Oslo-based Tribune Therapeutics has raised $40 million to advance its way of inhibiting the formation of scar tissue in disease. cen.acs.org/pharmaceutic... #chemsky🧪 #biosky

Conditional Activation of Protein Therapeutics by Templated Removal of Peptide Nucleic Acid Masking Groups Interleukin-2 (IL-2)-based therapeutics are emerging as treatments for immunotherapy; however, systemic activation of immune cells hampers their success. Chemically controlling the activity of potent...

TWeeP (This Week's Paper): Protecting groups for proteins? The Barnardes lab brilliantly uses a "lock"-PNA as a protein PG and the complementary "key"-PNA for deprotection via proximity-driven trans-thioesterification. Now out in @angewandtechemie.bsky.social.
onlinelibrary.wiley.com/doi/10.1002/...

Glucose-derived receptors for photo-controlled binding of amino acid esters in water - Communications Chemistry Selective amino acid receptors that operate in aqueous media are of interest for potential diagnostic and sensing applications. Here, the authors report glucose-derived photoswitchable receptors based...

TWeeP (This Week's Paper): Congratulations to my colleague Bartosz and Zibi on the nice work on glucose-derived bis-crownether receptors for photo-controlled binding of amino acid esters in water via isomerization of azobenzenes. Now out in @commschem.bsky.social.
www.nature.com/articles/s42...

Seeing the Spikes: The Future of Targetable Synthetic Voltage Sensors Measuring the transduction of electrical signals within neurons is a key capability in neuroscience. Fluorescent voltage sensitive dyes (VSDs) were early tools that complemented classical electrophysiology by enabling the optical recording of membrane potential changes from many cells simultaneously. Recent advances in the VSD field have led to bright and highly sensitive sensors that can be targeted to the desired cell populations in live brain tissue. Despite this progress, recently, protein-based genetically encoded voltage indicators (GEVIs) have become the go-to tools for targeted voltage imaging in complex environments. In this Perspective, we summarize progress in developing targetable VSDs, discuss areas where these synthetic sensors are or could become relevant, and outline hurdles that need to be overcome to promote the routine use of targetable VSDs in neuroscience research.

Voltage sensitive dyes are great tools for visualizing neuronal firing. Want to learn more about these sensors and how to target them to specific neurons in the brain? Read our Perspective (with Dali Sames and Dave Sulzer), now out in @pubs.acs.org ACS Chem. Neurosci.
pubs.acs.org/doi/10.1021/...

Proline cis/trans Conformational Selection Controls 14–3–3 Binding Intrinsically disordered protein regions (IDRs) are structurally dynamic yet functional, often interacting with other proteins through short linear motifs (SLiMs). Proline residues in IDRs introduce c...

TWeeP (This Week's Paper): Proline is a unique amino acid due to the thermodynamics and kinetics of the Xaa-Pro amide bond. In @pubs.acs.org JACS, @frederiktheisen.bsky.social et al. map out the role of cis-Pro in an intrinsically disordered region of the 14-3-3 protein.
pubs.acs.org/doi/10.1021/...

Triazination/IEDDA Cascade Modular Strategy Installing Pyridines/Pyrimidines onto Tyrosine Enables Peptide Screening and Optimization Modular chemical postmodification of peptides is a promising strategy that supports the optimization and innovation of hit peptide therapeutics by enabling rapid derivatization. However, current metho...

TWeeP (This Week's Paper): In @pubs.acs.org J. Am. Chem. Soc., Zuo et al. disclosed an innovative two-step tyrosine labeling–IEDDA reaction cascade: Tyrosine Triazine Ligation (YTL). PoC application in synthesis of a library of peptide-based dual-mode imaging probes.
pubs.acs.org/doi/abs/10.1...

Is Europe Running out of Chemistry Teachers? As shortages of qualified teachers plague schools, the chemical sciences community worries about who will inspire the next generation of scientists.

TWeeP (This Week's Paper): Is Europe Running out of Chemistry Teachers? ...a nice commentary by Vanessa Zainzinger from @cenmag.bsky.social in @pubs.acs.org ACS Central Science.
pubs.acs.org/doi/10.1021/...

A Protein Cleavage Platform Based on Selective Formylation at Cysteine Residues Site-selective cleavage of the peptide backbone in proteins is an important class of post-translational modification (PTM) in nature. However, the organic chemistry for such site-selective peptide bond cleavages has yet to be fully explored. Herein, we report cysteine S-formylation as a means of selective protein backbone cleavage. We developed N-formyl sulfonylanilide as a cysteine-selective formylation reagent for peptides and proteins. Upon S-formylation with the reagent, the amide bond adjacent to the S-formylated cysteine is cleaved by hydrolysis under neutral aqueous conditions. Formylation probes bearing a protein ligand enabled the affinity-based selective cleavage of the target proteins not only in the test tube but also under biorelevant conditions such as in crude cell lysate and on the cell surface. These results demonstrate the high biocompatibility of this protein cleavage technology. A proof-of-concept study of cleavage-induced protein activation further demonstrates its utility as a platform for the functional regulation of proteins by artificial PTM.

TWeeP (This Week's Paper): Selective protein cleavage under physiological conditions with a synthetic probe and no enzymes involved... sci-fi? No! Now a reality thanks to the cysteine formylation technology by Ojida, Hamachi and coworkers in JACS.
pubs.acs.org/doi/10.1021/...

A Malleable Collagen‐Mimic that Undergoes Moisture‐Induced Hardening for Gluing Hydrophilic Surfaces A collagen-inspired helical protein-mimic has been synthesized via topochemical polymerization of a designed tripeptide monomer. In the monomer crystal, molecules arrange in a head-to-tail manner, fo...

TWeeP (This Week's Paper): In @angewandtechemie.bsky.social Rai et al. disclosed a tripeptide with an N-terminal azide and C-alkyne that can undergo topochemical polymerization in its crystalline form. The material is good at gluing together biological matter.
onlinelibrary.wiley.com/doi/epdf/10....

Selective Protein (Post-)modifications through Dynamic Covalent Chemistry: Self-activated SNAr Reactions SNAr reactions were remarkably accelerated using a pretargeting and activating unit based on dynamic covalent chemistry (DCvC). A Cys attack at the C–F bond on the aromatic ring of salicylaldehyde derivatives was only observed upon iminium formation with a neighboring Lys residue of model small peptides. Such self-activation was ascribed to the stronger electron-withdrawing capability of the iminium bond with respect to that of the parent aldehyde that stabilized the transition state of the reaction, together with the higher preorganization of the reactive groups in the cationic aldiminium species. This approach was further applied for the functionalization of two antibodies. In both cases, the presence of the aldehyde group in close proximity to the reactive C–F bond resulted in a noteworthy increase in bioconjugation yields, with excellent chemo-selectivity. Whereas the modification of an IgG1 antibody led to stochastic product distributions, microenvironment selectivity was noted when employing IgG4, in line with the lower number of Lys residues in the hinge region of the latter. Additionally, the postfunctionalization of the modified antibodies was attained through the dynamic covalent exchange of the tethered iminium derivative with hydrazides, representing an unprecedented “tag and modify” selective bioconjugation strategy based on DCvC.

TWeeP (This Week's Paper): Happy new year! I'm back with my weekly highlights after the holiday break. Let's kick off 2025 with some nice bioconjugation work by Esteve, Koniev, Lehn et al. in #JACS. Dynamic imine formation triggers proximity-driven SNAr on proteins.
pubs.acs.org/doi/abs/10.1...

A Versatile “Synthesis Tag” (SynTag) for the Chemical Synthesis of Aggregating Peptides and Proteins Solid-phase peptide synthesis (SPPS) and native chemical ligation (NCL) are powerful methods for obtaining peptides and proteins that are otherwise inaccessible. Nonetheless, numerous sequences are di...

TWeeP (This Week's Paper): Challenging peptide sequence? Fear no more! SynTag from @ninahartrampf.bsky.social and coworkers is here to save the day! Read now, in J. Am. Chem. Soc.
pubs.acs.org/doi/10.1021/...