RSC - RSC Chem. Biol. latest articles

Post-translational Modifications of Silk Proteins

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D6CB00012F, Review Article

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Kota Nomura, Keiji Numata
Post-translational modifications (PTMs) endow silk proteins with chemical diversity that governs their higher-order assembly, hydration, and covalent connectivity. This review highlights the principal PTMs that define silk protein function, including...
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Comparative Analysis of Alkyne and Desthiobiotinylated Photoaffinity Probes for Chemotranscriptomic Profiling

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D6CB00030D, Paper

Open Access

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Daphne van den Homberg, Georgia Poulladofonou, Aurelia Dekens, Willem Velema
Understanding small molecule-RNA interactions is a crucial part in drug development and fundamental biology. Chemotranscriptomic profiling is emerging as a powerful platform to interrogate interactions of small molecules with entire...
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Photoclickable HaloTag Ligands for Spatiotemporal Multiplexed Protein Labeling on Living Cells

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D6CB00017G, Paper

Open Access

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Franziska Walterspiel, Begoña Ugarte-Uribe, Stefan Terjung, Alex Cabrera, Arif Ul Maula Khan, Claire Deo
Precise spatiotemporal control over fluorescence labeling is a powerful approach for selective marking and tracking of proteins of interest within living systems. Here, we report a photoclickable labeling platform based...
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Integration of Palladium-Catalyzed C-N Coupling into Self-Encoded Libraries for Accelerated Hit Discovery

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D5CB00303B, Paper

Open Access

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Sebastian Pomplun, Edith van der Nol, Zhenshuo Luo, Qing Qing Gao, Nils A Haupt, Sebastian Boecker
Affinity screenings with encoded libraries are transformative tools for rapid hit discovery from vast compound collections. Yet the adaptation of established chemical reactions to DNA-encoded libraries (DELs) remains challenging due...
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Development of a transcription factor-based biosensor strain for reporting α-terpineol production via the alcohol-dependent hemiterpene pathway in Escherichia coli

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D5CB00310E, Paper

Open Access

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Catherine A. Odhiambo, Isaac A. Ali, Gavin J. Williams
Development of a genetically-encoded biosensor enabled reporting production of α-terpineol in an engineered E. coli strain.
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Chemical modulation of the unfolded protein response reveals an antiviral role for the PERK pathway in human coronavirus 229E infection

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D5CB00242G, Paper

Open Access

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.

Isabella E Pellizzari-Delano, Trinity H Tooley, Debanjana Mondal, Keya Jani, Carla E Gallardo-Flores, Che C Colpitts
Broad spectrum antivirals are critical to respond rapidly to the threat posed by newly emerging RNA viruses. One potential candidate is the natural compound thapsigargin (Tg). Tg potently induces endoplasmic...
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Structure and characterisation of CMP-Kdn synthetase from the haptophyte microalgae Prymnesium parvum

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D5CB00285K, Paper

Open Access

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Claire Morley, Alexandra J. Munro-Clark, Ben A. Wagstaff, Irina Ivanova, Evgenia Dubinskaya, Ava Rostock, Mary Ortmayer, Colin W. Levy, Robert A. Field
Structural characterisation of a Kdn specific sialic acid synthetase, which can be utilised in the production of azide labelled sialic acid glycoconjugates.
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Discovery of natural products that modulate signaling in patient-derived cells

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D5CB00203F, Paper

Open Access

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Joseph A. Balsamo, Hannah L. Thirman, Kathryn E. Penton, Jordan T. Froese, Benjamin J. Reisman, Sierra M. Lima, Madeline J. Grider-Hayes, Chad R. Potts, Jonathan M. Irish, P. Brent Ferrell, Brian O. Bachmann
Many known natural products have been triaged from drug discovery pipelines based on results from single readout assays. Here we apply a multiplexed single cell approach for identifying new and known natural products with translational potential.
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Folded-State Compatibility and Unfolded-State Constraint Govern Staple-Based Stabilization: Guidelines from a Coiled-Coil Model

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D5CB00326A, Paper

Open Access

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Samantha C. Hatfield, Alexa N. Mattingley, Kayla K. Sujeta, Logan D. Humphrey, Taylor Crook, Hiram Aranda, Christian H. Freckleton, Joseph V. Clayson, Chase Renstrom, Joshua L. Price
Peptide stapling has emerged as a powerful strategy for stabilizing protein conformation, improving proteolytic resistance, and enhancing biomolecular recognition. Yet design principles for selecting staple sites remain elusive, so advances...
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Bifunctional glycolipids targeting TLR4‧MD-2 and short pentraxins

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D5CB00324E, Paper

Open Access

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Daniele Zucchetta, Lena Nuschy, Simon Gumpelmair, Peter Steinberger, Iain B. H. Wilson, Holger Heine, Alla Zamyatina
Innate immune detection of pathogen- and danger-associated molecular patterns (PAMPs/DAMPs) centres on pattern-recognition receptors, with the TLR4/MD-2 complex being uniquely sensitive to trace levels of lipopolysaccharide (LPS) as well as...
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Fluorescent Cationic Fluorinated Oxazoliniums for Cysteine Bioconjugation via S N Ar Reaction

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D5CB00289C, Paper

Open Access

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Karen Ka-Yan Kung, Yosephine Tania Limanto, Ajcharapan Tantipanjaporn, Jie-Ren Deng, Lai- Yi Tsang, Man Kin Wong
Using cationic fluorinated oxazolinium compounds, fluorescent cysteine-selective SNAr bioconjugation proceeds under mild conditions, resulting in fluorescent-labelled peptides and proteins with moderate to excellent conversions of up to 99%. Live cell...
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Enabling the synthesis of multi-payload thio-antibody conjugates through the use of pyridazinediones, p-anisidine derivatives and various click chemistries

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D6CB00018E, Paper

Open Access

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Clíona McMahon, Christophe J. Queval, Ioanna A. Thanasi, Dawn H. W. Lau, Michael Howell, Ning Wang, Maximillian T. W. Lee, Josephine S. Gaynord, James R. Baker, Vijay Chudasama
A strategy for constructing multi-payload thio-antibody conjugates using pyridazinedione scaffolds, para-anisidine derivatives, and various click chemistries.
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Tuning potency for precision: the role of the G4-ligand in G4-ligand conjugated oligonucleotides targeting individual G-quadruplex DNA structures

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D5CB00302D, Paper

Open Access

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Alva Abrahamsson, Sakina Khwaja, Andreas Berner, Rabindra Nath Das, Koit Aasumets, Namrata Chaudhari, Sjoerd Wanrooij, Erik Chorell
G4-ligands with varying chemical profiles were incorporated into G4-ligand conjugated oligonucleotides (GL-Os) and evaluated for G-quadruplex binding and stabilization, revealing how ligand chemistry shapes potency and specificity.
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Optical control of Cas9 activity through visible-light cleavable crRNAs

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D5CB00294J, Paper

Open Access

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Vanessa Hanff, Stepan Jerabek, Kim A. Langer, Robin Klimek, Janik Kaufmann, Jimin Kim, Dieter Egli, Alexander Heckel
Visible-light-cleavable crRNAs enable precise and non-invasive deactivation of Cas9 activity for safer genome editing.
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ILLUMINATING MICROTUBULAR FUNCTION WITH SMALL MOLECULES: PAST, PRESENT AND FUTURE OF FLUORESCENT TUBULIN-BINDING PROBES

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D5CB00321K, Review Article

Open Access

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Rebeca París-Ogáyar, Daniel Lucena-Agell, Karl-Heinz Altmann, Valle Palomo, J. Fernando Diaz
Developing tools for the real-time visualization of tubulin, microtubules, and their dynamics has been essential for studying key cellular processes such as cell division, migration, and differentiation. In this context,...
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Backbone engineering in the hydrophobic core of villin headpiece

RSC Chem. Biol., 2026, 7,226-232
DOI: 10.1039/D5CB00269A, Paper

Open Access

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Yuhan Lin, Ryley M. David, Dyllan M. Amin, Shane W. J. Osborne, W. Seth Horne
Engineering backbone composition in the hydrophobic core of the miniprotein villin headpiece yields a variant with ∼40% of its core residues modified that adopts an identical tertiary fold and shows enhanced conformational stability.
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Tuning the efficiency of molecular probes via quinone methide-based in situ labeling

RSC Chem. Biol., 2026, 7,208-215
DOI: 10.1039/D5CB00138B, Paper

Open Access

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Zachary Rabinowitz, Seyedehalaleh Anvar, Jun Liu, Zixin Chen, Yuzhao Zhang, Chao Cui, Ashton Sigler, Lina Cui
In this work, we tuned quinone-methide based fluorescent probes containing different phenol linker modifications using two logical chemical approaches to improve probe stability, protein-fluorophore adduct yield, and cellular retention and contrast.
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Contributors to the 2025 RSC Chemical Biology Emerging Investigators Collection

RSC Chem. Biol., 2026, 7,192-194
DOI: 10.1039/D5CB90052B, Profile

Open Access

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This article profiles the early career researchers whose work features in the RSC Chemical Biology Emerging Investigators Collection 2025.
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Expanding the actinomycetes landscape for phosphonate natural products through genome mining

RSC Chem. Biol., 2026, 7,298-312
DOI: 10.1039/D5CB00254K, Paper

Open Access

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Alina Zimmermann, Shu-Ning Xia, Julia Moschny, Juan Pablo Gomez-Escribano, Judith Boldt, Ulrich Nübel, Imen Nouioui, Janina Krause, Mattis Kreins Irle, William W. Metcalf, Chambers C. Hughes, Yvonne Mast
Screening 940 genome-sequenced actinomycetes revealed 54 strains with phosphonate BGCs; 17 inhibited a phosphonate-sensitive E. coli test strain, and 24 are likely novel phosphonate producers.
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Molecular characterisation of the acyltransferase-acyl carrier protein interface in a fungal highly reducing polyketide synthase

RSC Chem. Biol., 2026, 7,233-239
DOI: 10.1039/D5CB00278H, Paper

Open Access

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Mia E. Foran, Y. T. Candace Ho, Józef R. Lewandowski, Matthew Jenner
Scanning mutagenesis reveals the basis for molecular recognition between AT and ACP domains in fungal hrPKSs, providing a structural model for the complex, and highlighting that the AT domain transacylates ACPs from diverse hrPKS architectures.
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Sequence-specific fluorescence turn-on arises from base pairing-templated tautomerism in the tricyclic cytidine analogue DEAtC

RSC Chem. Biol., 2026, 7,216-225
DOI: 10.1039/D5CB00243E, Paper

Open Access

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Ana Shalamberidze, Harrison R. Pearce, Andrew L. Cooksy, Byron W. Purse
In solution and single-stranded DNA, ^DEAtC predominantly adopts a weakly emissive thymine-like tautomer, whereas base pairing with guanine or inosine stabilizes its bright cytidine-like tautomer, yielding a sequence-dependent fluorescence increase.
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DNA-programmed bispecific peptide assemblies for delivering cytotoxic payload to cells expressing EGFR and MET receptors

RSC Chem. Biol., 2026, 7,200-207
DOI: 10.1039/D5CB00238A, Paper

Open Access

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Pritam Ghosh, Huyen Dinh, Oliver Seitz
Interactions of bispecific DNA–peptide complexes with EGFR and MET on A549 cells showed a marked distance-affinity profile. The conditional cytotoxicity of constructs armed with auristatins is contingent on both targeting and cell internalisation.
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Heterologous biosynthetic crosstalk with the native mansouramycin cluster in Streptomyces albus Del14 reveals unexpected metabolites

RSC Chem. Biol., 2026, 7,240-249
DOI: 10.1039/D5CB00235D, Paper

Open Access

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Marc Stierhof, Liliya Horbal, Patrick Oberhäuser, Anja Palusczak, Peyton Cox, Maria Lopatniuk, Christopher Ruf, Josef Zapp, Andriy Luzhetskyy
Biosynthetic interactions between Streptomyces albus Del14 and heterologous gene clusters lead to the production of new metabolites.
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Differential regulation of SIRT5 activity by reduced nicotinic acid riboside (NARH)

RSC Chem. Biol., 2026, 7,286-297
DOI: 10.1039/D5CB00191A, Paper

Open Access

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Abu Hamza, Dickson Donu, Emily Boyle, Rasajna Madhusudhana, Alyson Curry, Yana Cen
NARH activates SIRT5 through allosteric binding, enhancing desuccinylase activity on physiological substrates.
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Subunit-specific isotope labelling of heteromeric complexes using cell-free protein expression: application to the 760 kDa ClpXP molecular machine

RSC Chem. Biol., 2026, 7,260-268
DOI: 10.1039/D5CB00259A, Paper

Open Access

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Astrid Audibert, Annelise Vermot, Mathieu Trauchessec, Karine Giandoreggio, Daphna Fenel, Aline Le Roy, Chloee Tymen, Basile Moscatello, Lauren Gandy, Caroline Mas, Lionel Imbert, Jerome Boisbouvier
An optimised, economical cell-free protocol for producing perdeuterated, methyl-labelled samples of the ClpXP machine, with separate labelling of the ClpX and ClpP components, enables the acquisition of high-resolution 2D methyl-TROSY NMR spectra.
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Late-stage peptide modification with salicylaldehyde tag enhances affinity for nuclear factor-kappa B essential modulator

RSC Chem. Biol., 2026, 7,195-199
DOI: 10.1039/D5CB00282F, Communication

Open Access

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Mattia Mason, Kaliroi Peqini, Federico Uggeri, Diego Rondelli, Sara Sattin, Luca Pignataro, Sara Pellegrino, Laura Belvisi, Edoardo Scarpa, Raffaella Bucci, Alberto Dal Corso
We introduce a versatile click-chemistry strategy for a tailored insertion of salicylaldehyde (SA) tags onto peptides, aimed at forming imine adducts with lysine residues on target proteins, thereby enhancing binding affinity and complex stability.
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Identification of mono-ADP-ribose readers using well-defined photoaffinity-based probes

RSC Chem. Biol., 2026, 7,250-259
DOI: 10.1039/D5CB00176E, Paper

Open Access

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Femke L. A. M. van der Heijden, Suzanne A. Weijers, Spyridoula Kondyli, Onno Bleijerveld, Michiel Vermeulen, Dmitri V. Filippov
This study introduces new photoaffinity-based probes to identify mono-ADP-ribose readers. Using human cell extracts, it detects both known and potential readers, thereby improving our understanding of mono-ADP-ribosylation.
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Optimization of the genetic code expansion technology for intracellular labelling and single-molecule tracking of proteins in genomically re-coded E. coli

RSC Chem. Biol., 2026, 7,269-285
DOI: 10.1039/D5CB00221D, Paper

Open Access

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Filip Ilievski, Linnea Wikström, Anneli Borg, Ivan L. Volkov, Gerrit Brandis, Magnus Johansson
Genetic code expansion (GCE) technology has been optimized, applied, and validated for single-molecule tracking (SMT) of intracellularly dye-labelled proteins in a fully re-coded E. coli strain.
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DNA-targeting Invader probes: discovery, principles and applications

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D5CB00286A, Review Article

Open Access

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Patrick J. Hrdlicka, Michaela E. Everly
Invader are double-stranded oligonucleotide probes with specific zippers of intercalator-functionalized nucleotides that enable efficient and highly specific recognition of complementary DNA regions via a strand-invasion mechanism.
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