RSC Chemical Biology最新文献_第8页

Rational design of an acridine-derived click chemistry-based artificial metallo-nuclease. 基于吖啶衍生物点击化学的人工金属核酸酶的合理设计。

IF 3.9

RSC Chemical Biology Pub Date : 2026-06-15 eCollection Date: 2026-08-05 DOI: 10.1039/d6cb00097e

Oliver Gould, Alex Gibney, Rebecca Lynn, Simon Poole, Bríonna McGorman, Andrew Kellett

{"title":"Rational design of an acridine-derived click chemistry-based artificial metallo-nuclease.","authors":"Oliver Gould, Alex Gibney, Rebecca Lynn, Simon Poole, Bríonna McGorman, Andrew Kellett","doi":"10.1039/d6cb00097e","DOIUrl":"10.1039/d6cb00097e","url":null,"abstract":"Artificial metallo-nucleases (AMNs) are metal complexes capable of cleaving nucleic acids and represent a promising therapeutic class. We recently established that copper(i)-catalysed azide-alkyne cycloaddition (CuAAC) click chemistry offers a versatile approach for building new minor groove targeting AMNs, epitomised by the tri-click (TC) series; here, three bidentate chelation sites comprising the N-triazole donor from the CuAAC reaction, together with the 'clicked' donor group, provide new ligand architectures that coordinate up to three bioactive copper(ii) metal ions. Although the TC series are promising scaffolds, no route has yet been established to direct, or enhance their DNA recognition properties. Herein, we report a new method for hybridising click chemistry-based AMNs with acridine, a potent DNA intercalating agent. Motivation for generating this conjugate stems from the opportunity to combine multimodal DNA binding properties, namely, DNA intercalation via the acridine unit, and minor groove recognition and cleavage by the nuclease component. Two sites of the original TC scaffold were retained for copper chelation and DNA cleavage, thereby producing a di-click-pyridine (DC-Py) unit, while the third site was repurposed for conjugation to the acridine (A) group. The resultant hybrid (DC-PyA) was then coordinated with copper(ii) ions (Cu2-DC-PyA) and the downstream direct and indirect DNA recognition properties and cleavage properties were examined, and activity resembling threading DNA intercalation was observed.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1605-1614"},"PeriodicalIF":3.9,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13326999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148377347","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

DNA origami-based drug delivery and cell manipulation: toward intelligent nanomedicine. 基于DNA折纸的药物传递和细胞操作：走向智能纳米医学。

IF 3.9

RSC Chemical Biology Pub Date : 2026-06-15 eCollection Date: 2026-08-05 DOI: 10.1039/d6cb00026f

Yuki Suzuki

{"title":"DNA origami-based drug delivery and cell manipulation: toward intelligent nanomedicine.","authors":"Yuki Suzuki","doi":"10.1039/d6cb00026f","DOIUrl":"10.1039/d6cb00026f","url":null,"abstract":"DNA origami has emerged as a versatile platform for constructing nanoscale architectures with precise shape programmability, molecular-level addressability, and dynamic structural reconfigurability. Since its introduction, DNA origami has evolved from a structural design method into a functional nanosystem capable of integrating molecular recognition, logic-gated operations, and mechanical motion, enabling a wide range of biomedical applications. This review outlines recent advances in DNA origami-based drug delivery and the regulation of cellular functions and cell fate. Strategic control over size, shape, and mechanical properties is discussed in the context of cellular uptake, intracellular behavior, and the efficient delivery of small-molecule drugs and nucleic acid therapeutics. Recent progress in dynamic DNA origami nanodevices and nanorobots that respond to molecular, chemical, or physical cues is highlighted, including systems that enable spatiotemporally controlled payload release and the nanoscale organization of membrane receptors to modulate cellular signaling. In addition, key stabilization strategies required for in vivo applications, such as covalent linking of constituent DNA strands and surface-coating methods, are summarized. Finally, future challenges and perspectives are discussed, emphasizing the growing role of chemical biology in endowing DNA origami with sensing, decision-making, and adaptive functions for intelligent nanomedicine.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1433-1443"},"PeriodicalIF":3.9,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13285921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148309783","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

Stabilized thioamide peptide agonists of the neuropeptide Y type 2 receptor for targeted cancer imaging. 神经肽Y型2受体的稳定硫酰胺肽激动剂用于靶向癌症成像。

IF 3.9

RSC Chemical Biology Pub Date : 2026-06-12 eCollection Date: 2026-08-05 DOI: 10.1039/d6cb00042h

Hoang Anh T Phan, Yanan Chang, Taylor M Barrett, Kristen E Fiore, Daniel Y Zhang, Ethan J Grove, E James Petersson

{"title":"Stabilized thioamide peptide agonists of the neuropeptide Y type 2 receptor for targeted cancer imaging.","authors":"Hoang Anh T Phan, Yanan Chang, Taylor M Barrett, Kristen E Fiore, Daniel Y Zhang, Ethan J Grove, E James Petersson","doi":"10.1039/d6cb00042h","DOIUrl":"10.1039/d6cb00042h","url":null,"abstract":"The neuropeptide Y type 2 receptor (Y2R) is highly expressed in human neuroblastoma and glioblastoma cells, and it has been shown to stimulate cancer cell growth. To develop an effective imaging probe for glioblastomas, peptide-based agents can be designed as Y2R agonists to be internalized by receptor-mediated endocytosis. However, the short half-life of most neuropeptides (<30 minutes) makes them unsuitable as imaging probes. Thioamide substitution, a single-atom O-to-S modification, is a promising tool to enhance peptide stability for therapeutic and imaging purposes. Herein, we designed and evaluated the first fluorescent cyclic thioamide peptides (HAP1 and HAP1-RS 33) as specific agonists and imaging agents of the Y2R. High-performance liquid chromatography and mass spectrometry were used to identify cleavage sites by analyzing peptides after incubating in mouse serum, confirming enhanced stability of the peptides. Our stabilized cyclized thiopeptide probe showed a significant improvement in half-life from approximately 30 minutes to over 8 hours while maintaining moderate potency and high selectivity for binding with Y2R receptor expressing cells, enabling selective imaging of Y2R-expressing neuroblastoma cells. These results show that thioamide stabilized cyclized peptide probes targeting specific receptors may have potential for use in different biological or clinical applications.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1597-1604"},"PeriodicalIF":3.9,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13262678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148253644","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, characterisation and application of an unspecific peroxygenase from Daldinia childiae. 水杨非特异性过氧酶的结构、表征及应用。

IF 3.9

RSC Chemical Biology Pub Date : 2026-06-11 eCollection Date: 2026-08-05 DOI: 10.1039/d6cb00141f

Alexander McKenzie, Claudia Clark, Katy A S Cornish, Jiacheng Li, Jack Domenech, Benjamin Melling, Miles P H Ralston, Jared Cartwright, Nicholas P Mulholland, William P Unsworth, Gideon Grogan

{"title":"Structure, characterisation and application of an unspecific peroxygenase from Daldinia childiae.","authors":"Alexander McKenzie, Claudia Clark, Katy A S Cornish, Jiacheng Li, Jack Domenech, Benjamin Melling, Miles P H Ralston, Jared Cartwright, Nicholas P Mulholland, William P Unsworth, Gideon Grogan","doi":"10.1039/d6cb00141f","DOIUrl":"10.1039/d6cb00141f","url":null,"abstract":"Unspecific peroxygenases (UPOs) have emerged as useful biocatalysts for the scalable and selective oxygenation of a large variety of organic molecules. UPOs have been divided into family I and family II enzymes, dependent upon sequence similarity and molecular weight, with family I being shorter in sequence. Here we report the characterisation and application of the family I UPO from Daldinia childiae (DchUPO). The enzyme was expressed in both Escherichia coli and Komagataella phaffii, yielding protein for kinetic and structural studies and biocatalytic application respectively. The structure of the enzyme revealed notable differences in the active site tunnel, compared with the well-studied family I artUPO, including F79 for V69 and F171 for I160. Notably, these differences were manifested in selectivity divergent from other UPOs when DchUPO was applied to preparative biotransformations; for example, (-)-menthol was converted exclusively into cis-6-hydroxymenthol in contrast to artUPO, which gave exclusively the tertiary alcohol 2,8-menthanediol.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1615-1620"},"PeriodicalIF":3.9,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13277406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148296718","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

De novo grafted coiled-coil peptides as p53/hDM2 inhibitors. 从头移植的卷曲肽作为p53/hDM2抑制剂。

IF 3.9

RSC Chemical Biology Pub Date : 2026-06-11 eCollection Date: 2026-08-05 DOI: 10.1039/d6cb00063k

Freya Spain, Diana Gimenez, Amanda M Acevedo-Jake, Bram Mylemans, Nikolas J Brooks, Boguslawa Korona, Danny T Huang, Thomas A Edwards, Aneika C Leney, Laura Itzhaki, Derek N Woolfson, Andrew J Wilson

引用次数: 0

Introducing azobenzenes as solid phase peptide synthesis linkers. 介绍偶氮苯作为固相肽合成连接剂。

IF 3.9

RSC Chemical Biology Pub Date : 2026-06-08 eCollection Date: 2026-08-05 DOI: 10.1039/d6cb00028b

Connor B Śmieja, Lizun Xin, Tianhui Tang, Ryan Tan, Martin Lee, Alison N Hulme

引用次数: 0

A non-canonical function of RNF8 opposes TRAF6-mediated stabilization of HIF1α. RNF8的非规范功能反对traf6介导的HIF1α稳定。

IF 3.9

RSC Chemical Biology Pub Date : 2026-06-08 eCollection Date: 2026-08-05 DOI: 10.1039/d5cb00209e

Larissa Ringelstetter, Elisabeth Mersdorf-Weber, Kenji Schorpp, Kamyar Hadian

{"title":"A non-canonical function of RNF8 opposes TRAF6-mediated stabilization of HIF1α.","authors":"Larissa Ringelstetter, Elisabeth Mersdorf-Weber, Kenji Schorpp, Kamyar Hadian","doi":"10.1039/d5cb00209e","DOIUrl":"10.1039/d5cb00209e","url":null,"abstract":"Ubiquitination is a central regulatory mechanism controlling protein stability and signaling in eukaryotic cells. The precise control of this machinery is crucial to avoid the development of diseases. Here, we identify a previously unrecognized interaction between the E3 ligase RNF8 and HIF1α, the oxygen-sensitive subunit of the hypoxia-inducible transcription factor HIF1. RNF8 antagonizes TRAF6-mediated stabilization of HIF1α under hypoxic conditions. Importantly, this regulatory effect is independent of the RNF8 E3 ligase activity but requires its forkhead-associated (FHA) domain. Yeast two-hybrid assays reveal an interaction between RNF8 FHA domain and the C-terminal transactivation domain (TAD) of HIF1α, despite the absence of a canonical FHA-binding motif in HIF1α. This interaction is maintained in a hydroxylation-deficient HIF1α mutant, indicating that prolyl hydroxylation is not required. Our findings suggest a non-canonical mode of FHA-dependent association by which RNF8 modulates HIF1α stability and downstream transcriptional control, with potential implications for hypoxia-driven signaling in triple-negative breast cancer.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1621-1631"},"PeriodicalIF":3.9,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13262263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148253538","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 γ-secretase complex: from discovery to a therapeutic target. γ-分泌酶复合物：从发现到治疗靶点。

IF 3.9

RSC Chemical Biology Pub Date : 2026-06-05 eCollection Date: 2026-08-05 DOI: 10.1039/d6cb00022c

Shweta R Malvankar, Michael S Wolfe

引用次数: 0

Thio-modification effects on mRNA translation using a PureCap-based capping method. 巯基修饰对基于purecapcap方法的mRNA翻译的影响。

IF 3.9

RSC Chemical Biology Pub Date : 2026-06-05 eCollection Date: 2026-07-08 DOI: 10.1039/d6cb00047a

Zheyu Meng, Yiwei Liu, Yuko Nakashima, Masahito Inagaki, Seigo Kimura, Yukari Kondo, Fumitaka Hashiya, Naoko Abe, Noriko Saito-Tarashima, Noriaki Minakawa, Yasuaki Kimura, Hiroshi Abe

{"title":"Thio-modification effects on mRNA translation using a PureCap-based capping method.","authors":"Zheyu Meng, Yiwei Liu, Yuko Nakashima, Masahito Inagaki, Seigo Kimura, Yukari Kondo, Fumitaka Hashiya, Naoko Abe, Noriko Saito-Tarashima, Noriaki Minakawa, Yasuaki Kimura, Hiroshi Abe","doi":"10.1039/d6cb00047a","DOIUrl":"10.1039/d6cb00047a","url":null,"abstract":"Controlling translational efficiency, stability, and innate immune recognition remains a critical challenge for the practical application of mRNA therapeutics, and chemical modification of nucleic acids is widely employed as an effective strategy to address these issues. Sugar modifications exemplified by 4'-thio substitution and phosphate-backbone modifications exemplified by phosphorothioate (PS) substitution can alter the behavior of nucleic acids. In this study, to introduce 4'-thio substitution and PS substitution at the +1 and +2 nucleotides of the 5' end of mRNA, we synthesized a series of cap analogs based on the PureCap method that we previously established, which enables preparation of highly pure capped mRNA for reliable evaluation of cap modification effects. Using the resulting cap analogs, mRNAs were prepared by in vitro transcription (IVT) with high-performance liquid chromatography (HPLC) purification, and even when modifications were introduced into the ribose moiety, IVT yields were not substantially reduced. In cultured HeLa cells, PS-modified mRNAs exhibited higher protein expression than the 4'-thio-modified counterparts for Cap 0, Cap 1, and Cap 2 structures. By contrast, for the Cap 2 structure, PureCap-derived mRNAs bearing either 4'-thio or PS modifications showed protein expression comparable to that of an N 1-methylpseudouridine (m1Ψ)-modified control mRNA prepared using the commercially available CleanCap AG, both at 72 h in the cell-based translation assay and at each measurement time point following subcutaneous administration in mice. Taken together, these results suggest that 4'-thio and PS modifications at the 5'-terminal +1 and +2 nucleotides can alter mRNA function. This work further demonstrates the utility of the PureCap platform and highlights its broad applicability for mRNA therapeutic development.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1309-1318"},"PeriodicalIF":3.9,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13251066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148228604","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

Methylation of DNA duplexes regulates cGAS-mediated innate immune activation via condensate formation. DNA双链甲基化通过凝析物形成调节cgas介导的先天免疫激活。

IF 3.9

RSC Chemical Biology Pub Date : 2026-06-04 eCollection Date: 2026-07-08 DOI: 10.1039/d6cb00059b

Kunihiko Morihiro, Manami Baba, Moeko Yamada, Akimitsu Okamoto

引用次数: 0