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Unravelling structure–function interactions between fluorinated heparan sulfate mimetics and signaling proteins† 揭示氟化硫酸乙酰肝素模拟物与信号蛋白之间的结构-功能相互作用。
IF 3.1
RSC Chemical Biology Pub Date : 2025-07-10 DOI: 10.1039/D5CB00174A
Virendrasinh Mahida, Rakesh Raigawali, Paula González, Ana Gimeno, Shani Leviatan Ben-Arye, Saurabh Anand, Sandhya Mardhekar, Jesús Jiménez-Barbero, Vered Padler-Karavani and Raghavendra Kikkeri
{"title":"Unravelling structure–function interactions between fluorinated heparan sulfate mimetics and signaling proteins†","authors":"Virendrasinh Mahida, Rakesh Raigawali, Paula González, Ana Gimeno, Shani Leviatan Ben-Arye, Saurabh Anand, Sandhya Mardhekar, Jesús Jiménez-Barbero, Vered Padler-Karavani and Raghavendra Kikkeri","doi":"10.1039/D5CB00174A","DOIUrl":"10.1039/D5CB00174A","url":null,"abstract":"<p >Fluorinated carbohydrates are emerging scaffolds in glycobiology, enabling the elucidation of the roles of the individual hydroxyl groups of a carbohydrate in protein binding and drug discovery. Herein, we report a divergent strategy to synthesize seven heparan sulfate (HS) mimetics featuring a fluorine atom at the C3 position of the glucuronic acid residue, with the objective of modulating structure–function relationships. The sensitivity of fluorine signals to sulfation patterns was confirmed <em>via</em><small><sup>19</sup></small>F-NMR spectroscopy, while <small><sup>3</sup></small><em>J</em><small><sub>HH</sub></small> coupling and NOE data demonstrated that the glucuronic acid residue retained its <small><sup>4</sup></small>C<small><sub>1</sub></small> conformation. Glycan microarray analysis and SPR binding studies revealed that a single hydroxyl-to-fluorine substitution in HS mimetics retains the binding of <em>N</em>-acetylated HS sequences for several growth factors and chemokines. Remarkably, GlcNAc6S-GlcA(3F) and GlcNS6S3S-GlcA(3F) exhibited binding properties comparable to those of highly <em>N</em>-sulfated native HS ligands. These findings provide valuable insights for the development of novel therapeutic agents targeting morphogens and cell signalling pathways.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 9","pages":" 1465-1472"},"PeriodicalIF":3.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144776461","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
Outstanding Reviewers for RSC Chemical Biology in 2024 2024年RSC化学生物学杰出审稿人
IF 3.1
RSC Chemical Biology Pub Date : 2025-07-08 DOI: 10.1039/D5CB90026C
{"title":"Outstanding Reviewers for RSC Chemical Biology in 2024","authors":"","doi":"10.1039/D5CB90026C","DOIUrl":"https://doi.org/10.1039/D5CB90026C","url":null,"abstract":"<p >We would like to take this opportunity to thank all of <em>RSC Chemical Biology</em>’s reviewers for helping to preserve quality and integrity in chemical science literature. We would also like to highlight the Outstanding Reviewers for <em>RSC Chemical Biology</em> in 2024.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 8","pages":" 1194-1194"},"PeriodicalIF":3.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/cb/d5cb90026c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740088","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
Signals from the sea: the structural peculiarity of lipid A and weak immunostimulatory lipopolysaccharide from Rheinheimera japonica† 海洋信号:日本莱茵海参脂质A和弱免疫刺激脂多糖的结构特性。
IF 3.1
RSC Chemical Biology Pub Date : 2025-07-07 DOI: 10.1039/D5CB00134J
Stefania De Chiara, Francesca Olmeo, Emanuela Andretta, Luca De Simone Carone, Marcello Mercogliano, Vlada S. Belova, Lyudmila A. Romanenko, Maxim S. Kokoulin, Alba Silipo, Antonio Molinaro and Flaviana Di Lorenzo
{"title":"Signals from the sea: the structural peculiarity of lipid A and weak immunostimulatory lipopolysaccharide from Rheinheimera japonica†","authors":"Stefania De Chiara, Francesca Olmeo, Emanuela Andretta, Luca De Simone Carone, Marcello Mercogliano, Vlada S. Belova, Lyudmila A. Romanenko, Maxim S. Kokoulin, Alba Silipo, Antonio Molinaro and Flaviana Di Lorenzo","doi":"10.1039/D5CB00134J","DOIUrl":"10.1039/D5CB00134J","url":null,"abstract":"<p >Lipopolysaccharides (LPSs) isolated from marine bacteria represent a valuable resource for biomedical innovation. Here, we report the first structural elucidation of the lipid A moiety and a preliminary immunological assessment of the full LPS from the marine Gram-negative <em>Rheinheimera japonica</em> KMM 9513<small><sup>T</sup></small>. Using MALDI-TOF mass spectrometry (MS) and tandem MS, we show that the lipid A from <em>R. japonica</em> KMM 9513<small><sup>T</sup></small> exhibits a heterogeneous architecture, composed of <em>mono</em>- and <em>bis</em>-phosphorylated tetra- and penta-acylated species with variations in the acyl chain length, saturation, branching, and positional isomerism. Functionally, the full LPS was found to be immunologically silent toward TLR4-mediated NF-κB activation in HEK-Blue™ hTLR4 cells and triggered only modest, dose-dependent responses in differentiated human THP-1 macrophages. Strikingly, the <em>R. japonica</em> LPS was able to antagonize <em>E. coli</em> LPS-induced TLR4 activation, even at low doses. Overall, this study uncovers a structurally and functionally atypical marine LPS with a dual profile, inactive towards TLR4 yet capable of modulating LPS-induced signaling. These findings offer a promising basis to consider <em>R. japonica</em> LPS as a source of structural inspiration for the design of synthetic derivatives with controlled immunological properties.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 9","pages":" 1414-1425"},"PeriodicalIF":3.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676018","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
Exploring the immunoproteasome's substrate preferences for improved hydrolysis and selectivity† 探索免疫蛋白酶体对改善水解和选择性的底物偏好。
IF 3.1
RSC Chemical Biology Pub Date : 2025-07-07 DOI: 10.1039/D5CB00114E
Christine S. Muli, Cody A. Loy and Darci J. Trader
{"title":"Exploring the immunoproteasome's substrate preferences for improved hydrolysis and selectivity†","authors":"Christine S. Muli, Cody A. Loy and Darci J. Trader","doi":"10.1039/D5CB00114E","DOIUrl":"10.1039/D5CB00114E","url":null,"abstract":"<p >The proteasome is an integral macromolecular machine responsible for regulated protein degradation, and its barrel-like core particle (CP) hydrolyzes protein substrates into peptide fragments. A proteasome isoform that is expressed under conditions of inflammation is known as the immunoproteasome (iCP), which incorporates different catalytic subunits of altered cleavage specificities from the standard proteasome (sCP). Probes and inhibitors have been generated to study iCP activity and for therapeutics, respectively; recently, the iCP has been harnessed as a prodrug enzyme to release bioactive compounds selectively into iCP-expressing cells. iCP-targeting probes, prodrugs, and inhibitors are based on peptide recognition sequences and their favorable interactions within the iCP's substrate channel. To better understand what unnatural substrates the iCP can recognize, we synthesized peptide-conjugated substrates and applied them to a liquid chromatography-mass spectrometry (LC-MS) method after incubation with purified human iCP. Structure–activity relationships of unnatural peptide-conjugated substrates revealed modifications that improved substrate selectively for the iCP by more than 3-fold compared to the original scaffold. As such, this report will be helpful to guide future iCP-targeting probes, prodrugs, and inhibitor design.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 8","pages":" 1306-1312"},"PeriodicalIF":3.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601775","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
Structure-guided engineering of a polyphosphate kinase 2 class III from an Erysipelotrichaceae bacterium to produce base-modified purine nucleotides† 从丹毒科细菌中提取的多磷酸激酶2类III的结构引导工程以产生碱基修饰的嘌呤核苷酸。
IF 3.1
RSC Chemical Biology Pub Date : 2025-07-07 DOI: 10.1039/D5CB00108K
Rachel M. Mitton-Fry, René Rasche, Ann-Marie Lawrence-Dörner, Jannik Eschenbach, Aileen Tekath, Andrea Rentmeister, Daniel Kümmel and Nicolas V. Cornelissen
{"title":"Structure-guided engineering of a polyphosphate kinase 2 class III from an Erysipelotrichaceae bacterium to produce base-modified purine nucleotides†","authors":"Rachel M. Mitton-Fry, René Rasche, Ann-Marie Lawrence-Dörner, Jannik Eschenbach, Aileen Tekath, Andrea Rentmeister, Daniel Kümmel and Nicolas V. Cornelissen","doi":"10.1039/D5CB00108K","DOIUrl":"10.1039/D5CB00108K","url":null,"abstract":"<p >Nucleobase-modified nucleoside-5′-triphosphates (NTPs) are important building blocks for the enzymatic synthesis of non-coding RNAs and mRNAs with improved properties. Chemical phosphorylation of base-modified nucleotides to NTPs remains challenging. Here, we report the enzymatic phosphorylation of purine-modified nucleoside-5′-monophosphates (NMPs) to the corresponding NTPs by the polyphosphate kinase 2 class III from an <em>Erysipelotrichaceae</em> bacterium (EbPPK2). The enzyme is highly promiscuous, accepting a range of NMPs with purine modifications. EbPPK2 efficiently catalyses the formation of the corresponding di-, tri- and tetraphosphates, typically with &gt;70% conversion to the NTP. Slower conversion was observed for analogues with oxo- or thio-substitutions at the C6-position. To better understand nucleotide binding and catalysis, we determined the crystal structure of EbPPK2 at 1.7 Å resolution bound to a non-hydrolysable ATP analogue and polyphosphate. This enabled structure-guided design of EbPPK2 variants that efficiently convert GMP analogues, while retaining activity for AMP. Apart from being the preferred industrial-scale ATP recycling catalyst, EbPPK2 and variants bear potential to become the favoured enzyme family for purine-modified NTP production.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 8","pages":" 1328-1335"},"PeriodicalIF":3.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12257356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643776","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
Correction: Turn-on fluorescent glucose transport bioprobe enables wash-free real-time monitoring of glucose uptake activity in live cells and small organisms 校正:开启荧光葡萄糖运输生物探针,可实现活细胞和小生物中葡萄糖摄取活性的无水洗实时监测。
IF 3.1
RSC Chemical Biology Pub Date : 2025-07-03 DOI: 10.1039/D5CB90030A
Monica S. Hensley, David Hutchings, Aldelrahman Ismail, Micaela Rayne Geborkoff, Thomas Werner and Marina Tanasova
{"title":"Correction: Turn-on fluorescent glucose transport bioprobe enables wash-free real-time monitoring of glucose uptake activity in live cells and small organisms","authors":"Monica S. Hensley, David Hutchings, Aldelrahman Ismail, Micaela Rayne Geborkoff, Thomas Werner and Marina Tanasova","doi":"10.1039/D5CB90030A","DOIUrl":"10.1039/D5CB90030A","url":null,"abstract":"<p >Correction for “Turn-on fluorescent glucose transport bioprobe enables wash-free real-time monitoring of glucose uptake activity in live cells and small organisms” by Monica S. Hensley <em>et al.</em>, <em>RSC Chem. Biol.</em>, 2025, <strong>6</strong>, 987–995, https://doi.org/10.1039/D4CB00239C.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 8","pages":" 1353-1353"},"PeriodicalIF":3.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576597","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
A dual-functional substrate for quantitation of substrate levels and GCase activity in living cells† 一种双功能底物,用于测定活细胞中底物水平和GCase活性。
IF 3.1
RSC Chemical Biology Pub Date : 2025-07-03 DOI: 10.1039/D5CB00045A
Ben Tiet, Sha Zhu, Xi Chen, Nadia Anastasi, Nicholas W. See, Matthew C. Deen, Eva Harde and David J. Vocadlo
{"title":"A dual-functional substrate for quantitation of substrate levels and GCase activity in living cells†","authors":"Ben Tiet, Sha Zhu, Xi Chen, Nadia Anastasi, Nicholas W. See, Matthew C. Deen, Eva Harde and David J. Vocadlo","doi":"10.1039/D5CB00045A","DOIUrl":"10.1039/D5CB00045A","url":null,"abstract":"<p >Loss of function mutations in the gene <em>GBA1</em>, which encodes the lysosomal glycoside hydrolase β-glucocerebrosidase (GCase) cause Gaucher's disease (GD). Moreover, one mutant allele of <em>GBA1</em> is the most common genetic risk factor for the development of Parkinson's disease (PD). To gain a better understanding how these mutations drive development of PD and how GCase is regulated within cells, the field needs chemical reporters of GCase activity that can be used within living cells. Fluorogenic substrates are one method that can be used to quantify enzyme activities within cells yet existing substrates for GCase have limitations. In particular, the inability to monitor cellular uptake of substrate limits the ability to disentangle impairments in uptake of substrate from impairments in lysosomal GCase activity. Here we report on the preparation and biological characterisation of LysoRF-GBA – a new chemical tool which can be used to quantitatively measure both the cellular levels of intact substrate and lysosomal GCase activity within lysosomes. We demonstrate that, by using LysoRF-GBA, endogenous GCase activity can be measured within live neuroblastoma cells. The selectivity of this substrate for GCase, relative to other cellular enzymes, was validated by genetic and pharmacological perturbation of GCase. By using LysoRF-GBA and concomitantly monitoring levels of both cleaved product and intact substrate, we were able to measure GCase engagement with a known pharmacological chaperone and discriminate between pharmacological agents that affect GCase activity from those that impair endocytosis. Further, the ability to monitor intracellular levels of intact LysoRF-GBA also enabled us to measure its time dependent accumulation within cells, providing insight into when steady state levels of this substrate are reached. LysoRF-GBA therefore shows high potential to be exploited as a tool for the discovery of compounds that could beneficially modulate its activity for benefit in diseases including PD.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 8","pages":" 1297-1305"},"PeriodicalIF":3.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576596","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
A biparatopic HER2-targeting ADC constructed via site-specific glycan conjugation exhibits superior stability, safety, and efficacy† 通过位点特异性聚糖偶联构建的双异位her2靶向ADC具有优越的稳定性、安全性和有效性。
IF 3.1
RSC Chemical Biology Pub Date : 2025-06-25 DOI: 10.1039/D5CB00096C
Qi Xue, Jianjian Peng, Wenying Dai, Qingsong Wu, Jinbiao Jiao, Yudi Hu, Wanxing Sha, Yang Yang, Wenhao Yu, Siyang Liu, Ting Xu and Jie P. Li
{"title":"A biparatopic HER2-targeting ADC constructed via site-specific glycan conjugation exhibits superior stability, safety, and efficacy†","authors":"Qi Xue, Jianjian Peng, Wenying Dai, Qingsong Wu, Jinbiao Jiao, Yudi Hu, Wanxing Sha, Yang Yang, Wenhao Yu, Siyang Liu, Ting Xu and Jie P. Li","doi":"10.1039/D5CB00096C","DOIUrl":"10.1039/D5CB00096C","url":null,"abstract":"<p >HER2 is overexpressed in approximately 15–20% of cancers and is associated with aggressive disease progression. We developed JSKN003, a bispecific HER2-targeted antibody–drug conjugate (ADC), through site-specific conjugation technology based on <em>N</em>-glycosylation engineering. JSKN003 maintains a biantennary glycan structure and exhibits superior structural homogeneity, optimized hydrophilicity, and reduced aggregation compared to conventional thiol-maleimide chemistry. In preclinical models JSKN003 demonstrated potent antitumor efficacy, inducing tumor regression in multiple HER2-expressing tumors, such as NCI-N87, BxPC-3, and PDX tumor models. Mechanistically, JSKN003 binds specifically to HER2, undergoes efficient internalization, and traffics to the lysosome, where the payload DXd is released, leading to DNA damage and apoptosis. JSKN003 retained its cytotoxic activity against trastuzumab-resistant cells, attributed to efficient payload delivery and blockade of downstream HER2 signaling pathways, demonstrating the potential to overcome clinical trastuzumab resistance. The safety profile of JSKN003 was evaluated in cynomolgus monkeys and was found to be acceptable, with no severe toxicities observed at therapeutic doses. JSKN003 demonstrated excellent antitumor activity and a favorable safety profile in clinical trials, highlighting its potential as a promising therapeutic option for patients with HER2-positive tumors. These findings suggest that JSKN003 could be a valuable therapeutic strategy with excellent efficacy and safety for HER2-expressing tumors in the clinical setting.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 8","pages":" 1284-1296"},"PeriodicalIF":3.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508786","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 SpyBLI cell-free pipeline for the rapid quantification of binding kinetics from crude samples† SpyBLI无细胞管道用于原油样品结合动力学的快速定量。
IF 3.1
RSC Chemical Biology Pub Date : 2025-06-23 DOI: 10.1039/D5CB00079C
Olga Predeina, Misha Atkinson, Oliver Wissett, Montader Ali, Cristina Visentin, Stefano Ricagno, Anthony H. Keeble, Mark R. Howarth and Pietro Sormanni
{"title":"The SpyBLI cell-free pipeline for the rapid quantification of binding kinetics from crude samples†","authors":"Olga Predeina, Misha Atkinson, Oliver Wissett, Montader Ali, Cristina Visentin, Stefano Ricagno, Anthony H. Keeble, Mark R. Howarth and Pietro Sormanni","doi":"10.1039/D5CB00079C","DOIUrl":"10.1039/D5CB00079C","url":null,"abstract":"<p >Accurate measurements of binding kinetics, encompassing equilibrium dissociation constant (<em>K</em><small><sub>D</sub></small>), association rate (<em>k</em><small><sub>on</sub></small>), and dissociation rate (<em>k</em><small><sub>off</sub></small>), are critical for the development and optimisation of high-affinity binding proteins. However, such measurements require highly purified material and precise ligand immobilisation, limiting the number of binders that can be characterised within a reasonable timescale and budget. Here, we present the SpyBLI method, a rapid and cost-effective biolayer interferometry (BLI) pipeline that leverages the SpyCatcher003–SpyTag003 covalent association, eliminating the need for both binder purification and concentration determination. This approach allows for accurate binding-kinetic measurements to be performed directly from crude mammalian-cell supernatants or cell-free expression blends. We also introduce a linear gene fragment design that enables reliable expression in cell-free systems without any PCR or cloning steps, allowing binding kinetics data to be collected in under 24 hours from receiving inexpensive DNA fragments, with minimal hands-on time. We demonstrate the method's broad applicability using a range of nanobodies and single-chain antibody variable fragments (scFvs), with affinity values spanning six orders of magnitude. By minimising sample preparation and employing highly controlled, ordered sensor immobilisation, our workflow delivers reliable kinetic measurements from crude mixtures without sacrificing precision. We expect that the opportunity to carry out rapid and accurate binding measurements in good throughput should prove especially valuable for binder engineering, the screening of next-generation sequencing–derived libraries, and computational protein design, where large numbers of potential binders for the same target must be rapidly and accurately characterised to enable iterative refinement and candidate selection.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 8","pages":" 1313-1327"},"PeriodicalIF":3.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627374","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
Regulation of bacterial phosphorelay systems 细菌磷接力系统的调控。
IF 3.1
RSC Chemical Biology Pub Date : 2025-06-19 DOI: 10.1039/D5CB00016E
Daniel M. Foulkes, Daniel M. Cooper, Catherine Westland and Dominic P. Byrne
{"title":"Regulation of bacterial phosphorelay systems","authors":"Daniel M. Foulkes, Daniel M. Cooper, Catherine Westland and Dominic P. Byrne","doi":"10.1039/D5CB00016E","DOIUrl":"10.1039/D5CB00016E","url":null,"abstract":"<p >In terms of biomass, bacteria are the most successful organisms on earth. This is partly attributed to their tremendous adaptive capabilities, which allows them to sense and rapidly organise responses to changing environmental stimuli. Using complex signalling mechanisms, bacteria can relay cellular information to fine-tune their metabolism, maintain homeostasis, and trigger virulence processes during infection. Across all life, protein phosphorylation represents the most abundant signalling mechanism, which is controlled by a versatile class of enzymes called protein kinases and their cognate phosphatases. For many years, histidine kinase (HK)-containing two-component systems (TCSs) were considered the canonical instruments of bacterial sensing. However, advances in metagenomics has since proven that bacterial phosphorelay is in fact orchestrated by a functionally diverse array of integrated protein kinase types, including Ser, Thr, Tyr and Arg-targeting enzymes. In this review, we provide an up-to-date appraisal of bacterial kinase signalling, with an emphasis on how these sensing pathways are regulated to modulate kinase output. Finally, we explore how selective kinase inhibitors may be exploited to control infections and combat the looming health emergency of multidrug resistant bacteria.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 8","pages":" 1252-1269"},"PeriodicalIF":3.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508787","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
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