RSC Chemical Biology最新文献_第3页

Harnessing the promiscuity of a nonulosonic acid synthase for the chemoenzymatic synthesis of pseudaminic acid derivatives and specificity mapping of an anti-Pse antibody. 利用非醛酸合酶的乱交性合成假胺衍生物和特异性定位抗pse抗体。

IF 3.9

RSC Chemical Biology Pub Date : 2026-09-07 eCollection Date: 2026-10-08 DOI: 10.1039/d6cb00217j

Natasha E Hatton, Niccolay Madiedo Soler, Ethan D Goddard-Borger, Martin A Fascione

引用次数: 0

Multivalent peptides for blood-brain barrier translocation, cell penetration and microRNA-21 inhibition in glioblastoma. 胶质母细胞瘤中血脑屏障易位、细胞渗透和microRNA-21抑制的多价肽。

IF 3.9

RSC Chemical Biology Pub Date : 2026-09-01 DOI: 10.1039/d6cb00229c

Talhat Chaudhry, Marco Cavaco, Vera Neves, Miguel A R B Castanho, Lauren Tonge, Francesca Giuntini, Adam Schofield, Christopher R Coxon, Kehinde Ross

{"title":"Multivalent peptides for blood-brain barrier translocation, cell penetration and microRNA-21 inhibition in glioblastoma.","authors":"Talhat Chaudhry, Marco Cavaco, Vera Neves, Miguel A R B Castanho, Lauren Tonge, Francesca Giuntini, Adam Schofield, Christopher R Coxon, Kehinde Ross","doi":"10.1039/d6cb00229c","DOIUrl":"10.1039/d6cb00229c","url":null,"abstract":"Glioblastoma (GBM) is an aggressive brain cancer for which the prognosis remains poor despite the advances in our understanding of the complex heterogeneity of the disease. Therapeutic access to GBM tumours requires drugs to cross the blood-brain barrier (BBB), a physiological obstacle that restricts the passage of compounds from systemic circulation into the brain. Blood-brain barrier peptide shuttles (BBBpS), which are a subclass of cell penetrating peptides (CPPs), represent a promising approach for transferring large cargos across the BBB, especially cargos such as peptides or antisense oligonucleotides against RNA targets. Such RNA targets include microRNAs (miRNA), of which several have emerged as candidate drug targets in GBM. MicroRNA-21 is one such miRNA implicated in GBM, and although peptide-based miR-21 inhibition has been reported, delivery of peptide-based inhibitors of miR-21 across the BBB has received limited attention. Here, we selected a BBB-penetrating peptide, SYPGWSW, for conjugation to a peptide-based inihibitor of miRNA processing. We show that SYPGWSW penetrates GBM cell lines and its function depends critically on the properties of aromatic residues Tyr and Trp but not on Pro residues. Further, subsitution of Tyr with unnatural amino acids cyclohexylalanine or 1-naphthylalanine enhanced the internalisaton of the parent peptide by 2 to 4 fold. Mechanistically, the higher level of uptake was associated with enhanced stability of the peptide, which appeared to be partly associated with binding to human serum albumin. Finally we showed that a peptide inhibitor of miR-21 processing conjugated to SYPGWSW traversed an in vitro BBB model and enabled the functional silencing of miR-21-5p in GBM cells. Together, these findings pave the way for peptide conjugates as novel therapeutics for silencing miRNA expression in brain cancer.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13584092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chemistry and biology of oxidatively damaged RNA nucleotides. 氧化损伤RNA核苷酸的化学和生物学。

IF 3.9

RSC Chemical Biology Pub Date : 2026-09-01 eCollection Date: 2026-10-08 DOI: 10.1039/d6cb00143b

Kasturi Raorane, Marlies Weber, Virginie Marchand, Mark Helm, Yuri Motorin

{"title":"Chemistry and biology of oxidatively damaged RNA nucleotides.","authors":"Kasturi Raorane, Marlies Weber, Virginie Marchand, Mark Helm, Yuri Motorin","doi":"10.1039/d6cb00143b","DOIUrl":"10.1039/d6cb00143b","url":null,"abstract":"Nucleic acid damage under oxidative stress conditions is a well-established phenomenon relevant to evolution of all living organisms. While well investigated for DNA, cellular RNAs are also a subject of extensive damage, featuring similar reactivity towards reactive oxygen species generated by external factors and cellular metabolism. The chemistry of DNA and RNA oxidative damage is rather complex, involving a variety of concomitant chemical reactions which are further exacerbated by secondary reactions that increase the already overwhelming list of chemically damaged nucleotides. The damage is of random character, typically resulting in sub-stoichiometrically damaged sites. This substantially complicates the analysis of RNA oxidation. Modern analytical techniques include deep sequencing-based protocols allowing precise mapping of such damaged residues in cellular RNAs. Increasing experimental evidence suggests vast and widespread biological consequences and highlights the importance of the metabolism of oxidized RNA in a variety of cellular processes. The main effects are expected at the level of translation, since all key players of the translational machinery, mRNA, rRNA and tRNAs are prominent oxidation targets. In this review we present current achievements in the analysis of RNA oxidation/damage chemistry, traditional and modern methods allowing RNA oxidation analysis and current view on the biological consequences of RNA oxidation in the living cell.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1867-1896"},"PeriodicalIF":3.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

14-3-3/Tau molecular glues modulate in vitro tau condensation. 14-3-3/Tau分子胶在体外调节Tau凝聚。

IF 3.9

RSC Chemical Biology Pub Date : 2026-08-28 eCollection Date: 2026-10-08 DOI: 10.1039/d6cb00156d

Maxime C M van den Oetelaar, Leandre Ravatt, Francisco Maqueda Zelaya, Ansgar Oberheide, Tom R van de Wijngaart, Floor M A van Boxtel, Marloes A M Pennings, Carlo J A Verhoef, Thijs W van Veldhuisen, Peter J Cossar, Christian Ottmann, Susanne Wegmann, Luc Brunsveld

引用次数: 0

Use of conformationally locking antisense oligonucleotides for the targeted inhibition of precursor microRNAs. 利用构象锁定反义寡核苷酸靶向抑制前体microrna。

IF 3.9

RSC Chemical Biology Pub Date : 2026-08-24 eCollection Date: 2026-10-08 DOI: 10.1039/d6cb00158k

Megan N Westwood, Sicong Ma, Aiden J Saunders, Samantha A Howden, Sarah C Keane

{"title":"Use of conformationally locking antisense oligonucleotides for the targeted inhibition of precursor microRNAs.","authors":"Megan N Westwood, Sicong Ma, Aiden J Saunders, Samantha A Howden, Sarah C Keane","doi":"10.1039/d6cb00158k","DOIUrl":"10.1039/d6cb00158k","url":null,"abstract":"Antisense oligonucleotides (ASOs) are widely used as therapeutics. One class of ASOs enhances protein expression by sequestering the mature microRNA (miRNA) in a double-stranded structure within the RNA-induced silencing complex (RISC). An alternative approach for the targeted control of gene expression is to use ASOs that bind to precursor miRNAs (pre-miRNAs) and modulate their enzymatic processing. Here, we demonstrate that ASOs that disrupt the junction of pre-miR-31, a region we previously identified as a critical regulatory element, are potent inhibitors of Dicer/TRBP processing in vitro but do not inhibit Dicer/TRBP binding. Furthermore, we extend and validate this strategy to pre-miR-144, which has a similar junction-dependent structure-function relationship. Through analysis of pre-miRNA secondary structures, we find that nearly 20% of human pre-miRNAs are predicted to contain junctions, and we validate our ASO approach on several members of this group. Importantly, we also verify the application of junction-targeting ASOs for the specific inhibition of pre-miRNA processing in cellulo. Our study reemphasizes the important role of RNA structure in regulating Dicer/TRBP processing of pre-miRNAs and provides the framework to develop structure-informed ASOs that serve to inhibit miRNA production.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"2040-2052"},"PeriodicalIF":3.9,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Selective oxidation and quantification of m5C in ribonucleosides and RNA in an epigenetic context. 表观遗传背景下核糖核苷和RNA中m5C的选择性氧化和定量。

IF 3.9

RSC Chemical Biology Pub Date : 2026-08-21 eCollection Date: 2026-10-08 DOI: 10.1039/d6cb00203j

Kora Holschbach, Tobias Walter, Davide Guglielminotti, Annika Menke, David Schmidl, Doreen Reuter, Ken Kögel, Lola Stroh, Sabine Schneider, Pascal Giehr, Thomas Carell, Lena Daumann

{"title":"Selective oxidation and quantification of m5C in ribonucleosides and RNA in an epigenetic context.","authors":"Kora Holschbach, Tobias Walter, Davide Guglielminotti, Annika Menke, David Schmidl, Doreen Reuter, Ken Kögel, Lola Stroh, Sabine Schneider, Pascal Giehr, Thomas Carell, Lena Daumann","doi":"10.1039/d6cb00203j","DOIUrl":"10.1039/d6cb00203j","url":null,"abstract":"Selective modification of methylated bases in RNA and DNA is central to the field of epigenetics and furthermore fundamental for developing next-generation sequencing and liquid biopsy applications. While in DNA the detection and modification of 5-methylcytidine (5mdC) is fairly advanced, current strategies for detecting this modification (m5C) in RNA face significant technical challenges. Chemical conversion methods, such as bisulfite sequencing, remain widely used but induce substantial degradation of RNA and DNA, leading to incomplete conversion and reduced sequence complexity. Here we demonstrate the first example of a TET-biomimetic, selectively oxidizing the C-H bond of the methyl group in m5C in RNA. We also developed an isotope-labelling mass spectrometry-based strategy for quantification of the hydroxymethyl- (hm5C), formyl- (f5C) and carboxy-derivatives (ca5C), respectively. By changing substrate and iron complex ratios and the reaction time, the product spectrum can be tuned to obtain either more f5C or ca5C as a product. The iron complex' ligand system can be further modified to fine-tune product yields and distribution.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"2080-2090"},"PeriodicalIF":3.9,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery and evolution of an (R)-selective transaminase for production of sitagliptin. 西格列汀生产的(R)选择性转氨酶的发现和进化。

IF 3.9

RSC Chemical Biology Pub Date : 2026-08-20 eCollection Date: 2026-10-08 DOI: 10.1039/d6cb00180g

Matthew Treadell, Gareth R E Surman, Grayson J Ford, Christopher W Otun, Shiny Joseph Srinivasan, James Galman, Maria Bawn, Akash Pandya, Craig J Markin, Anthony P Green, Jack S Rowbotham

{"title":"Discovery and evolution of an (R)-selective transaminase for production of sitagliptin.","authors":"Matthew Treadell, Gareth R E Surman, Grayson J Ford, Christopher W Otun, Shiny Joseph Srinivasan, James Galman, Maria Bawn, Akash Pandya, Craig J Markin, Anthony P Green, Jack S Rowbotham","doi":"10.1039/d6cb00180g","DOIUrl":"10.1039/d6cb00180g","url":null,"abstract":"We report the discovery and engineering of a new (R)-selective transaminase (RTA-223, UniProt W9Z089), identified from Capronia coronata. The wild-type enzyme was found to display broad activity on a range of bulky aryl and alkyl ketone substrates, with high enantioselectivity using both d-alanine and isopropyl amine as amine donors. We then investigated activity towards pro-sitagliptin ketone, a well-known challenging pharmaceutical target of industrial significance. Although no forward amination of pro-sitagliptin was initially detected by wild-type RTA-223, low-level activity in the reverse deamination reaction enabled engineering without the need for truncated sitagliptin analogues. Adopting this reverse screening strategy, two active-site mutations unlocked forward amination activity, and subsequent rounds of directed evolution delivered a quadruple mutant (H53L/V60G/F113A/V148A) capable of converting pro-sitagliptin to (R)-sitagliptin with high levels of stereoselectivity (e.r. 93 : 7). We further performed a kinetic analysis of the candidates from across the evolution process, using a previously reported coupled assay system linked to d-alanine oxidation. This work validates reverse screening as an effective approach for evolving transaminases toward sterically hindered substrates and highlights RTA-223 as a promising candidate for further biocatalyst development.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"2053-2058"},"PeriodicalIF":3.9,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148799033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RNA modifications and RNA-binding proteins: interactions, regulation, and new avenues for therapeutic modulation. RNA修饰和RNA结合蛋白：相互作用、调控和治疗调节的新途径。

IF 3.9

RSC Chemical Biology Pub Date : 2026-08-20 eCollection Date: 2026-10-08 DOI: 10.1039/d6cb00136j

Gabriela Vega-Hernández, Amanda L Garner

{"title":"RNA modifications and RNA-binding proteins: interactions, regulation, and new avenues for therapeutic modulation.","authors":"Gabriela Vega-Hernández, Amanda L Garner","doi":"10.1039/d6cb00136j","DOIUrl":"10.1039/d6cb00136j","url":null,"abstract":"RNA-binding proteins (RBPs) are central regulators of post-transcriptional gene expression, recognizing RNAs through sequence, structure, and chemical modifications. Post-transcriptional RNA modifications, including m6A, m1A, m5C, m7G, and pseudouridine (Ψ), form the epitranscriptome, a dynamic regulatory layer that modulates RNA stability, localization, and translation. These modifications are interpreted by specialized \"reader\" RBPs that translate epitranscriptomic marks into functional outcomes. Dysregulation of RNA modifications or their associated reader RBPs has been increasingly linked to the development of cancers, neurological disorders, and other diseases, highlighting their potential for therapeutic manipulation. This review summarizes key RNA modifications and regulating RBPs with a specific emphasis on how dysregulation can lead to cancers. We further discuss current approaches for investigating and manipulating reader RBP-RNA interactions, highlighting how these methods enable new opportunities for therapeutic discovery.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1921-1942"},"PeriodicalIF":3.9,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13512903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The red box: a selective G-quadruplex binder that downregulates c-MYC expression in human cells. 红框：一种选择性g -四重体结合物，下调人类细胞中c-MYC的表达。

IF 3.9

RSC Chemical Biology Pub Date : 2026-08-18 eCollection Date: 2026-09-02 DOI: 10.1039/d5cb00329f

Paula Novo, Iván Montes de Oca, Claudia García-Delgado, Agustín Sánchez-Temprano, Elena Pazos, Carlos Peinador

{"title":"The red box: a selective G-quadruplex binder that downregulates c-MYC expression in human cells.","authors":"Paula Novo, Iván Montes de Oca, Claudia García-Delgado, Agustín Sánchez-Temprano, Elena Pazos, Carlos Peinador","doi":"10.1039/d5cb00329f","DOIUrl":"10.1039/d5cb00329f","url":null,"abstract":"G-quadruplex (G4) structures within oncogene promoters represent promising therapeutic targets, particularly in the context of transcriptional regulation. Here, we report that the red box, a fully organic macrocyclic cationic receptor, exhibits high affinity and selectivity for G4 structures. Biophysical analyses reveal that the red box binds the c-MYC G4 with nanomolar affinity. Notably, the red box displays greater selectivity for c-MYC over duplex DNA compared to the well-characterized porphyrin TMPyP4, and its macrocyclic architecture is essential for this activity, as its acyclic analogue displays negligible G4 stabilization. In cellular assays, treatment with non-cytotoxic concentrations of the red box selectively downregulated c-MYC expression in HEK293T cells, with minimal effects on c-KIT and hTERT. Unlike previously reported G4-selective ligands based on Pd(ii)/Pt(ii) metallacycles, the red box achieves nanomolar affinity and selectivity through a fully metal-free, hydrazone-based scaffold, addressing key limitations related to cost, biodegradability, and long-term biocompatibility. Furthermore, c-MYC downregulation was consistently observed across multiple cell lines, including tumour-derived cellular models, underscoring the translational relevance of this new class of organic G4 binders.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1743-1750"},"PeriodicalIF":3.9,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13483072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148799012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Kinase cascades: emerging design principles and guidelines. 激酶级联：新兴的设计原则和指导方针。

IF 3.9

RSC Chemical Biology Pub Date : 2026-08-14 eCollection Date: 2026-10-08 DOI: 10.1039/d6cb00196c

Ruth Nussinov, Clil Regev, Hyunbum Jang

引用次数: 0