RSC - RSC Chem. Biol. latest articles

A fluorescence-activated droplet sorting assay for ultra-high-throughput screening of PET hydrolases based on a pH indicator

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D6CB00122J, Paper

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Maxine Yew, Haizhen Bi, Dingjie Wang, Rui Qi, Huiling Yuan, Huanhuan Zhai, Gen Li, Qinhong Wang, Leilei Zhu
Ultra-high-throughput screening of PET hydrolases enabled by a pH-based fluorescence-activated droplet sorting (FADS) assay.
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Prochelators modulate azole activity against Candida albicans in a metal-dependent manner

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D6CB00073H, Paper

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Madeline Ann Merriman, Catherine A. Denning-Jannace, Andrea Barboza Hurtado, Francesca A. Vaccaro, Yu-Shien Sung, Elisa Tomat, Katherine J. Franz
Candida albicans is an opportunistic fungal pathogen of growing clinical concern, in part due to antifungal drug tolerance.
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De novo acyl carrier proteins display structure-independent modification and sequence novelty

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D5CB00148J, Paper

Open Access

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Michael Andrés Herrera, Grace King, Zoe Ozols, Gioele Tiburtini, Nicoletta Schiavo, Francesca Spyrakis, Louise Charkoudian, Dominic James Campopiano
Acyl carrier proteins (ACPs) are dynamic, structurally conserved α-helical proteins central to many primary and secondary metabolic processes. Whilst prior engineering efforts have focused on strategic mutagenesis and “helix swaps”,...
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Development of a Spectrophotometric Assay for High-Throughput Screening and Mechanistic Characterization of Glucose-1-Phosphate Thymidylyltransferase Inhibitors

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D6CB00002A, Paper

Open Access

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Bronwyn E Rowland, Jesse C Fuller, David L Jakeman
The sugar β-L-rhamnose is often a conserved component of bacterial polysaccharide capsules, an extracellular structure featured in many drug-resistant, pathogenic bacteria. The β-L-rhamnose biosynthetic enzymes (RmlA-D) have therefore become key...
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Mixed squaramide thioesters as phosphate group analogues for non-competitive antagonists of the phospholipid-sensing G protein-coupled receptor GPR55

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D5CB00231A, Paper

Open Access

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Junpei Abe, Xianyue Huang, Nozomi Ishii, Itaru Imayoshi, Yoshio Hirabayashi, Ichiro Matsuo, Hiroyuki Kamiguchi, Yukishige Ito, Adam T. Guy, Peter Greimel
High-affinity inhibitors of specific receptors are a valuable tool to elucidate cellular signaling, control biological systems and develop therapeutic drugs.
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Decoding Protein–Phospholipid Interaction Networks in Cancer: The Role of Acyl-Chain Remodeling

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D6CB00015K, Review Article

Open Access

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Berit Blume, Grace Potter, Carsten Schultz, Andrew Emili
Lipids, particularly phosphoinositides, are increasingly recognized as important markers and causal regulators in cancer progression. Less appreciated, however, are the functional consequences of changes in phospholipid acyl chain length and...
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Backbone N-Heteroatom Substitution as a Strategy to Enhance Peptide Proteolytic Stability

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D6CB00061D, Paper

Open Access

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Avraz F Anwar, Natalia Cano-Sampaio, Juan Del Valle
Peptide-based ligands are well-suited to engage large biomolecular surfaces but are often limited by rapid proteolytic degradation in biological environments. Backbone modification offers a direct means to disrupt protease recognition...
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Igalan Attenuates Sepsis-Induced Inflammation through Covalent Targeting of the NLRP3 Inflammasome Pathway

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D5CB00280J, Paper

Open Access

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Chengchen Hou, Yang Chen, Wenjie Bi, Lin Gao, Simiao Yu, Xiaowen Zhang, Zekun Chen, Tiantian Wei, Dilnoza Dusmatova, Rimma F Мukhamatkhanova, Ildar D Sham'yanov E, Liwen Han, Zhi-Yuan Lu, Hua Wang, Nilufar Z. Mamadalieva, Kewu Zeng
Macrophages play a critical role in sepsis, a life-threatening systemic inflammatory syndrome that necessitates urgent therapeutic intervention. Unfortunately, no approved drugs currently target this specific pathological mechanism. In this study,...
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A cysteine reactive chloroalkane probe enables HaloTag ligation for downstream chemical proteomics analysis

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D6CB00004E, Paper

Open Access

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Rubaba R. Abanti, Dongqing Wu, Pavel Kielkowski
Abanti et al. describe the application of the HaloTag protein in a chemical proteomics workflow. HaloTag facilitates fast and highly specific conjugation with probe labelled proteins, allowing downstream shift-assay, pull-down and proteomics.
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Strategies to Overcome Hepatic Clearance of Endogenous Proteins – Molecular and Formulation Approaches

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D6CB00041J, Review Article

Open Access

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Kirstin Meiners, Tobias Stepic, Lorenz Meinel, Tessa Lühmann
The medical use of biologics is often limited by rapid elimination from circulation. This review explores formulation strategies for enhancing the pharmacokinetic profiles of therapeutic proteins with hepatic clearance as...
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Methylene insertion reveals importance of phosphate-phosphate distance in DNase I cleavage

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D6CB00024J, Paper

Open Access

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Ayano Nagaya, Kohji Seio, Yoshiaki Masaki
DNase I is a major endonuclease in human serum that cleaves double-stranded DNA. While its activity has been characterized for sequence preference and structural requirements, the effects of chemical modifications...
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Leveraging the lipoprotein trafficking pathway for the development of novel antimicrobials

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D6CB00009F, Review Article

Open Access

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Haley B. Gartrell, Taryn Trigler, Marcin Grabowicz, William M. Wuest
The lipoprotein trafficking pathway and the known small-molecule inhibitors. The molecules depicted are enterololin, lolamicin, abaucin, and fendiline which target LolF and LolE within A. baumannii and E. coli.
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Keap1-Kelch-targeting protein–protein interaction inhibitors, but not reversibly-binding electrophiles, increase the thermostability of Keap1 in the cellular environment

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D6CB00045B, Paper

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Sharadha Dayalan Naidu, Dina Dikovskaya, Jasmine M. Walker, Charlotte Lim Jia Yee, Annamarie J. Cafferkey, Manaka Tatsuno, Jialin Feng, Terry W. Moore, Tatum Johnson, Tadashi Honda, Geoff Wells, Takafumi Suzuki, Masayuki Yamamoto, Albena T. Dinkova-Kostova
Keap1-Kelch-targeting protein–protein interaction inhibitors (left) increase the thermostability of Keap1-mCherry, whereas double Michael acceptors (right) decrease the thermostability of Keap1-mCherry in the cellular environment.
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Enhancing mRNA Stability and Translational Potential Through Tailored Modifications at the 3' End

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D6CB00033A, Paper

Open Access

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Olga Perzanowska, Joanna Kowalska, Jacek Jemielity
Poly(A) tails regulate mRNA turnover and translation through multiple RNA–protein interactions, and deadenylation is the initiating step of the major cytoplasmic decay pathways. Here, we report a simple post-transcriptional strategy...
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Influence of linker design on the stability, folding, and assembly of tethered collagen-mimetic peptides

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D5CB00298B, Paper

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Debasis Ghosh, Anthony R. Perez, S M Mobin Sikder, Jesus R. Vasquez, Claire Zhang, Anjan Maity, Tao Ye, Andrea D. Merg
We explore the effects of linker length and linker composition on the stability, folding, and assembly of molecularly tethered collagen-mimetic peptides (CMPs).
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Lipid droplet dynamics in metabolic regulation

RSC Chem. Biol., 2026, 7,517-535
DOI: 10.1039/D6CB00081A, Review Article

Open Access

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Ralf Weiskirchen, Sabine Weiskirchen, Amedeo Lonardo
Lipid droplets are dynamic organelles for lipid storage and metabolic signaling. This review summarizes their biogenesis and turnover, tissue-specific roles in metabolic disease, and therapeutic targeting opportunities.
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Synthesis of siRNAs containing carbocyclic nucleotides and the role of cyclopentane conformation in RNAi activity

RSC Chem. Biol., 2026, 7,590-595
DOI: 10.1039/D6CB00038J, Communication

Open Access

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Jayanta Kundu, Dhrubajyoti Datta, Masaaki Akabane-Nakata, Soham Mandal, Monika Krampert, Martin Egli, Muthiah Manoharan
5′-(E)- and 5′-(Z)-vinylphosphonate carbocyclic DNA and 5′-(E)-vinylphosphonate 2′- and 3′-O-methyl carbocyclic RNAs were incorporated at 5′ termini of antisense strands of small interfering RNAs.
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Development of PROTACs for targeted degradation of oncogenic TRK fusions

RSC Chem. Biol., 2026, 7,596-614
DOI: 10.1039/D6CB00008H, Paper

Open Access

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Saurav Kumar, Jiewei Jiang, Mia S. Donald-Paladino, Joy Chen, Andrea Gutierrez, Alexander J. Federation, Frank Szulzewsky, Eric C. Holland, Fleur M. Ferguson, Behnam Nabet
JWJ-01-378 recruits cereblon (CRBN) to induce potent and selective degradation of oncogenic TRK fusions, leading to a collapse in signaling and loss of cancer cell viability. Graphic was created using https://biorender.com.
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Post-translational modifications of silk proteins

RSC Chem. Biol., 2026, 7,576-589
DOI: 10.1039/D6CB00012F, Review Article

Open Access

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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.
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Comparative analysis of alkyne- and desthiobiotinylated photoaffinity probes for chemotranscriptomic profiling

RSC Chem. Biol., 2026, 7,641-648
DOI: 10.1039/D6CB00030D, Paper

Open Access

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Daphne A. L. van den Homberg, Georgia Poulladofonou, Aurelia Dekens, Willem A. Velema
The suitability of desthiobiotin and alkyne modified Ribocil photoaffinity probes for chemotranscriptomic profiling were compared. Desthiobiotin appears to unselectively interact with RNA, rendering it unfavorable for transcriptome-wide studies.
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Photoclickable Halotag ligands for spatiotemporal multiplexed protein labeling on living cells

RSC Chem. Biol., 2026, 7,729-736
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
A novel photoclickable HaloTag ligand enables multicolor spatiotemporal labeling of proteins on the surface of living cells.
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Integration of palladium-catalyzed C–N coupling into self-encoded libraries for accelerated hit discovery

RSC Chem. Biol., 2026, 7,630-640
DOI: 10.1039/D5CB00303B, Paper

Open Access

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Edith van der Nol, Zhenshuo Luo, Qing Qing Gao, Nils Alexander Haupt, Sebastian Böcker, Sebastian Pomplun
We expanded the self-encoded library (SEL) platform via C–N cross-couplings, testing 170+ building blocks and generating a 25.725-member library. We established automated MS/MS decoding and demonstrated robust hit enrichment in screens against CAIX.
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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., 2026, 7,708-723
DOI: 10.1039/D5CB00242G, Paper

Open Access

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Isabella E. Pellizzari-Delano, Trinity H. Tooley, Debanjana Mondal, Keya Jani, Carla E. Gallardo-Flores, Che C. Colpitts
Broad spectrum host-targeting antivirals are critical to respond rapidly to newly emerging RNA viruses.
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Structure and characterisation of CMP-Kdn synthetase from the haptophyte microalgae Prymnesium parvum

RSC Chem. Biol., 2026, 7,686-694
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, 7,669-685
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., 2026, 7,737-750
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.
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Fluorescent cationic fluorinated oxazoliniums for cysteine bioconjugation via an SNAr reaction

RSC Chem. Biol., 2026, 7,724-728
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
A new series of fluorescent fluorinated oxazoliniums were developed for cysteine-selective bioconjugation via S_NAr under mild conditions.
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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, 7,695-707
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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Illuminating microtubule functions with small molecules: past, present and future of fluorescent tubulin-binding probes

RSC Chem. Biol., 2026, 7,536-575
DOI: 10.1039/D5CB00321K, Review Article

Open Access

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R. París-Ogáyar, D. Lucena-Agell, K.-H. Altmann, V. Palomo, J. F. Díaz
Fluorescent tubulin-targeting agents: from probe development to applications and strategies for next-generation ligands.
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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, 7,615-629
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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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, 7,656-668
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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Optical control of Cas9 activity through visible-light cleavable crRNAs

RSC Chem. Biol., 2026, 7,649-655
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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RNA-binding Landscape of Amiloride: Large-scale Profiling and Structural Basis of U–U Mismatch Recognition

RSC Chem. Biol., 2025, Accepted Manuscript
DOI: 10.1039/D6CB00055J, Paper

Open Access

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Kosuke Tsuzuki, Kazumitsu Onizuka, Momo Okada, Ryosuke Nagasawa, Emi Miyashita, Kaoru R. Komatsu, Hirohide Saito, Jiro Kondo, Fumi Nagatsugi
Amiloride possesses a characteristic chemical scaffold capable of recognizing uracil (U) through three complementary hydrogen bonds; however, its binding selectivity toward naturally occurring RNA structural motifs has remained uncharacterized. In...
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A green enzymatic route for the biotransformation of naphthalene to phthalic acid

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D6CB00050A, Paper

Open Access

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Yang Huang, Maxine Yew, Suxin Huang, Haifeng Liu, Leilei Zhu
Biotransformation of naphthalene into phthalic acid via an in vitro multi-enzyme cascade reaction.
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Structural and biochemical insights into the inhibition of Mycobacterium tuberculosis cyclic dinucleotide phosphodiesterase by a sulfur-modified cyclic dinucleotide analog

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D6CB00006A, Paper

Open Access

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Dagur Singh Hanuman, Singh Neeharika, Sinha Krishna Murari, Simpa K. Yeboah, Herman O. Sintim, Eerappa Rajakumara
ES-cAAMP binds to Mtb CdnP in a unique horseshoe conformation in the catalytic pocket (CG-site) away from the catalytic cation and residues, which are in the R-site. It competes with the substrate and inhibits CdnP's catalytic activity.
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Intricacies in iron–sulfur cluster function and biogenesis: functional versatility, sulfur sources, and enzyme specificity

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D5CB00330J, Review Article

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Sarah M. Spigelmyer, Patricia C. Dos Santos
Iron–sulfur clusters associate with proteins to perform diverse constitutive and transient functions in biological systems. Five distinct pathways have been described for the synthesis and maturation of Fe–S clusters in prokaryotic species.
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Heck-type C-glycosylations in the synthesis of artificial nucleotides and functional nucleic acids

RSC Chem. Biol., 2026, Advance Article
DOI: 10.1039/D6CB00078A, Review Article

Open Access

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Robert Dörrenhaus, Andre Zenz, Stephanie Kath-Schorr
Heck-reaction-mediated C-glycosylation enables efficient access to diverse artificial DNA nucleosides, supporting advanced studies of structure, function, and fluorescent nucleobase probes.
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