ChemBioChem最新文献_第4页

Versatile Enzymatic Approach for Truncation, Labeling, and Mutation of Nucleobase-Modified Aptamers Demonstrated on Indole-Modified β-Conglutin Aptamer. 吲哚修饰β-粘连蛋白适配体证明了核碱基修饰适配体的截断、标记和突变的多功能酶方法。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-26 DOI: 10.1002/cbic.202500534

Marek Ondruš, Pablo Alberto Franco-Urquijo, Teresa Mairal Lerga, Lucie Mužíkova Čechová, M Carmen Bermudo Redondo, Ciara K O Sullivan, Michal Hocek

{"title":"Versatile Enzymatic Approach for Truncation, Labeling, and Mutation of Nucleobase-Modified Aptamers Demonstrated on Indole-Modified β-Conglutin Aptamer.","authors":"Marek Ondruš, Pablo Alberto Franco-Urquijo, Teresa Mairal Lerga, Lucie Mužíkova Čechová, M Carmen Bermudo Redondo, Ciara K O Sullivan, Michal Hocek","doi":"10.1002/cbic.202500534","DOIUrl":"https://doi.org/10.1002/cbic.202500534","url":null,"abstract":"A new enzymatic method for truncation of aptamers from 5'-end has been developed and demonstrated on a newly selected indole-modified β-conglutin aptamer. This method relies on extension of a primer containing ribonucleotides, which can be specifically hydrolyzed by RNase, thereby removing the whole or 5'-part of the primer. This approach enables flexible synthesis of modified aptamers truncated from the 5' end, 3' end, or both ends-a capability previously achievable only through chemical oligonucleotide synthesis. Furthermore, by employing doubly labeled primers, diverse labeled or modified nucleotides are introduced to prepare 5'-labeled aptamers suitable for fluorescence- or immobilization-based assays. The different variations of this method also enable the synthesis of mutated sequences to study the effect of modifications and their positions. Overall, this enzymatic method provides a valuable alternative for the truncation or labeling of (hyper)modified and functional oligonucleotides avoiding the need for chemical synthesis.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500534"},"PeriodicalIF":2.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advanced Antibody-Drug Conjugates Design: Innovation in Linker Chemistry and Site-Specific Conjugation Technologies. 先进的抗体-药物偶联设计：连接化学和位点特异性偶联技术的创新。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-26 DOI: 10.1002/cbic.202500305

Yutaka Matsuda, Jenny R Chang, Brian A Mendelsohn

{"title":"Advanced Antibody-Drug Conjugates Design: Innovation in Linker Chemistry and Site-Specific Conjugation Technologies.","authors":"Yutaka Matsuda, Jenny R Chang, Brian A Mendelsohn","doi":"10.1002/cbic.202500305","DOIUrl":"https://doi.org/10.1002/cbic.202500305","url":null,"abstract":"Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapies, with the potential to improve treatment precision because of their unique mechanism of selectively delivering cytotoxic payloads (PLs) to tumor cells. ADCs combine a monoclonal antibody directed against a tumor-associated antigen with a potent cytotoxic PL via a covalent linker which connects the PL to the antibody. Several ADCs have been approved for clinical use in oncology, including Mylotarg, Adcetris, Kadcyla, Besponsa, Polivy, Lumoxiti, Padcev, Enhertu, Trodelvy, Aidixi, Zynlonta, Tivdak, Elahere, Datroway, and Emrelis. This review focuses on recent advances in linker chemistry and site-specific conjugation technologies, which are critical for optimizing ADC design and improving therapeutic indices. The development of next-generation ADCs has focused on overcoming challenges related to linker stability, efficiency of target antigen internalization, and pharmacokinetics. Traditional conjugation methods, such as lysine or cysteine conjugation, have been widely used but are associated with inherent issues of heterogeneity and instability. Advances in linker chemistry, such as the development of novel cleavable linkers, have significantly contributed to the clinical success of ADCs. In this review, different linker components are discussed, including chemical handles for conjugation, spacers to improve hydrophobicity, and triggers for PL release. In addition, innovative conjugation strategies are highlighted, which enhance ADC homogeneity and stability. The site-specific conjugation and therapeutic performance benefits of technologies such as THIOMAB, SMARTag, microbial transglutaminase, glycan remodeling, and AJICAP are discussed. The toxicity profiles of ADCs and strategies are also addressed to mitigate off-target effects and systemic toxicity. Overall, this review provides a comprehensive overview of the current state of linker and conjugation technologies in ADC development.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500305"},"PeriodicalIF":2.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biocompatible Metal Sulfide-Based Nanomaterials for Antimicrobial and Wound Healing Applications. 用于抗菌和伤口愈合的生物相容性金属硫化物基纳米材料。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-26 DOI: 10.1002/cbic.202500604

Ashmalina Rahman, Mohammad Mansoob Khan

引用次数: 0

Functional Analysis of Histidine-Dependent Self-Cleaving RNAs Obtained by In Vitro Selection. 组氨酸依赖性自裂rna的体外筛选功能分析。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-23 DOI: 10.1002/cbic.202500411

Nae Sakimoto, Shoichiro Tanaka, Riki Hatakenaka, Yoshie Yamaguchi-Miyazaki, Elisa Tomita-Sudo, Tomoka Akita, Taku Ishigaki, Shigenori Iwai, Junji Kawakami

{"title":"Functional Analysis of Histidine-Dependent Self-Cleaving RNAs Obtained by In Vitro Selection.","authors":"Nae Sakimoto, Shoichiro Tanaka, Riki Hatakenaka, Yoshie Yamaguchi-Miyazaki, Elisa Tomita-Sudo, Tomoka Akita, Taku Ishigaki, Shigenori Iwai, Junji Kawakami","doi":"10.1002/cbic.202500411","DOIUrl":"https://doi.org/10.1002/cbic.202500411","url":null,"abstract":"Ribozymes, ribonucleic acids with enzymatic functions, have not yet been practically used in nucleic acid medicine, possibly due to their low activity levels. We hypothesized that functional RNAs with high activity can be obtained by mimicking the catalytic reactions of ribonuclease A. We aimed to obtain histidine-dependent functional RNAs from an RNA library using in vitro selection with L-histidine. An RNA library with a random sequence of 70 nucleotides was constructed and used. A self-cleaving RNA (I-04) with histidine specificity and a rate constant of kobs(I-04) = 4.6 × 10-3 (min-1) at pH 5.0 was obtained. Owing to its low activity, reselection was performed. II-28, obtained on the second selection, showed cleavage activity in the presence of histidine, but not with histidine analogs. The rate constant of II-28 was kobs(II-28) = 3.0 × 10-3 (min-1) at pH 5.0, comparable to that of I-04. The activity of these molecules, however, is very low and different from that of ribonuclease A. Several histidine-dependent and divalent metal ion-independent self-cleaving RNAs were obtained. The pH profile of the RNAs suggested that histidine was not utilized as a catalytic residue, but histidine was presumed to be working in the formation of the active structure.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500411"},"PeriodicalIF":2.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Review of Polyhydroxybutyrate Biosynthesis by Different Microorganisms. 不同微生物合成聚羟基丁酸酯的研究进展。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-23 DOI: 10.1002/cbic.202500562

Linjing Jia, Mairui Zhang, Deepak Kumar, Jikai Zhao

{"title":"A Review of Polyhydroxybutyrate Biosynthesis by Different Microorganisms.","authors":"Linjing Jia, Mairui Zhang, Deepak Kumar, Jikai Zhao","doi":"10.1002/cbic.202500562","DOIUrl":"https://doi.org/10.1002/cbic.202500562","url":null,"abstract":"Polyhydroxybutyrate (PHB) production from renewable biomass feedstocks using microorganisms provides a sustainable alternative to petroleum-based plastics, addressing critical challenges such as plastic pollution and fossil fuel consumption. Unlike previous reviews that primarily focus on single genera or metabolic mechanisms, this review provides a comprehensive comparison of multiple microbial platforms, emphasizing strain selection strategies, genetic engineering approaches, and substrate flexibility, particularly for waste valorization. Bacterial systems, while efficient, are limited by the high cost of sterile conditions. Engineered yeasts and fungi offer resilience to industrial stresses but face metabolic constraints. In addition, haloarchaeal extremophiles have gained attention for PHB synthesis under high-salinity, nonsterile conditions, offering unique advantages for cost-effective bioprocessing. Photosynthetic microorganisms integrate CO2 capture with PHB synthesis but face challenges like slow growth rates and low yields. Mixed microbial cultures provide a cost-effective approach by utilizing low-cost substrates under nonsterile conditions, though optimizing enrichment strategies remain essential to improving productivity. Future directions highlight the significance of evaluating strain selection strategies, advancing genetic engineering approaches, and scaling up production processes. Additionally, assessing technoeconomic viability and life-cycle environmental impact is crucial to support the development of PHB as a scalable, cost-effective, and environmentally friendly solution for the circular economy.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500562"},"PeriodicalIF":2.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nature-Inspired Chemical Probes for Labeling tRNAs Containing 2-Thiouridine (s²U). 自然启发化学探针标记含有2-硫脲（s2U）的trna。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-23 DOI: 10.1002/cbic.202500453

Hongling Zhou, Yuanyuan Li, Jingwen Zhang, Li Wang, Ya Ying Zheng, Chengze Wu, Thomas J Begley, Jia Sheng, Rui Wang

引用次数: 0

Aldehyde or Hydrate? Investigation into the Oxidation of 5-Formylcytosine Derivatives Using a Computational and Experimental Approach. 醛还是水合？用计算和实验方法研究5-甲酰基胞嘧啶衍生物的氧化反应。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-23 DOI: 10.1002/cbic.202500480

Kuangjie Liu, Annika Menke, Fabian L Zott, Domenic Mayer, Lena J Daumann, Hendrik Zipse

{"title":"Aldehyde or Hydrate? Investigation into the Oxidation of 5-Formylcytosine Derivatives Using a Computational and Experimental Approach.","authors":"Kuangjie Liu, Annika Menke, Fabian L Zott, Domenic Mayer, Lena J Daumann, Hendrik Zipse","doi":"10.1002/cbic.202500480","DOIUrl":"https://doi.org/10.1002/cbic.202500480","url":null,"abstract":"This study investigates the oxidation of 5-hydroxymethyl and 5-formyl nucleobases using an iron(IV)-oxido complex that mimics the function of TET enzymes. A central question in this context is whether the oxidation of formyl substrates proceeds via the aldehyde or the hydrate form. To investigate the possible different reaction kinetics of these two forms, nucleobases containing a 6-aza-moiety are employed, giving rise to significantly more aldehyde hydrate as compared to the unaltered nucleobase. The concentration changes of substrates and products during oxidation were followed with 1H NMR spectroscopy. To analyze the kinetics of the oxidation reactions, a detailed numerical simulation of the stepwise sequential oxidation process is applied. 5-Hydroxymethyl nucleobases are first oxidized to the respective 5-formyl derivatives, which exist in equilibrium with their hydrate forms, and then further oxidized to the final 5-carboxyl nucleobases. The rate constants for 5-hydroxymethyl nucleobase oxidation show a good correlation with CH bond dissociation values. The influence of hydrate formation on sequential oxidation is most prominent in the 6-aza-derivatives. The results not only deepen our understanding of substrate oxidation by iron-oxido species but also pave the way for future studies on related biological oxidation mechanisms.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e70085"},"PeriodicalIF":2.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oleanolic Acid Amide Derivatives as 20s Proteasome Stimulators 齐墩果酸酰胺衍生物作为20s蛋白酶体刺激剂。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-19 DOI: 10.1002/cbic.202500199

Jaida M. Osman, Duno S. Dantis, Hanna King, Darci Jones Trader

引用次数: 0

Front Cover: Pathological Disulfide Bond Crosslinking: Molecular Insights into Amyloidogenesis and Diseases Progression (ChemBioChem 18/2025) 封面：病理二硫键交联：淀粉样蛋白发生和疾病进展的分子见解（ChemBioChem 18/2025）

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-19 DOI: 10.1002/cbic.70050

Dong Min Kang, Nataliia Lukianenko, Ja-Hyun Baik, Yun Kyung Kim, Sungsu Lim

引用次数: 0

Hydrogen-Deuterium Exchange Defines Ligand-Induced Conformational Changes to the Class III Biotin Protein Ligase from Saccharomyces cerevisiae. 氢-氘交换定义了配体诱导的酿酒酵母III类生物素蛋白连接酶的构象变化。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-17 DOI: 10.1002/cbic.202500439

Louise M Sternicki, Tara L Pukala, Kamila J Pacholarz, Perdita Barran, Grant W Booker, Steven W Polyak, Kate L Wegener

{"title":"Hydrogen-Deuterium Exchange Defines Ligand-Induced Conformational Changes to the Class III Biotin Protein Ligase from Saccharomyces cerevisiae.","authors":"Louise M Sternicki, Tara L Pukala, Kamila J Pacholarz, Perdita Barran, Grant W Booker, Steven W Polyak, Kate L Wegener","doi":"10.1002/cbic.202500439","DOIUrl":"https://doi.org/10.1002/cbic.202500439","url":null,"abstract":"Biotin protein ligase (BPL) catalyzes the covalent attachment of biotin onto biotin-dependent enzymes, where it functions as an essential cofactor. Eukaryotic BPLs are distinct due to the presence of a large N-terminal extension to the conserved catalytic domain and C-terminal cap. No high-resolution structures of a eukaryotic BPL have been solved; however, previous functional studies revealed the N-terminal extension interacts with the biotinylation substrate. Mass spectrometry (MS) and complementary techniques were utilized to investigate the structure of the yeast Saccharomyces cerevisiae BPL (ScBPL). Lower resolution techniques suggested holo-ScBPL had a more compact structure and sampled fewer conformational states. In addition, solution-phase and a charge state dependent gas-phase stabilization was observed. Hydrogen-deuterium exchange (HDX) MS provided experimental validation of the AlphaFold predicted structure of ScBPL, with a folded domain structurally homologous to a glutamine amidotransferase identified in the N-terminal extension, and a mostly homologous catalytic domain to that of other species' BPLs. Further HDX analyses identified localized conformational changes in the ScBPL active site and N-terminal domain that occur concomitantly with ligand binding. These data provide novel insights into the unique structure of a class III BPL and how ligands influence this structure for catalysis of protein biotinylation.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500439"},"PeriodicalIF":2.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0