ChemBioChem最新文献_第8页

Sequence Context in DNA i-Motifs Can Nurture Very Stable and Persistent Kinetic Traps. DNA i-Motifs中的序列内涵可以培育非常稳定和持久的动力学陷阱。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-06 DOI: 10.1002/cbic.202400647

Alexander S Minasyan, Merlin Peacey, Te'Kara Allen, Irina V Nesterova

引用次数: 0

Machine learning guided rational design of a non-heme iron-based lysine dioxygenase improves its total turnover number. 机器学习指导下的非血红素铁基赖氨酸二氧化酶合理设计提高了其总周转次数。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-06 DOI: 10.1002/cbic.202400495

R Hunter Wilson, Daniel J Diaz, Anoop Rama Damodaran, Ambika Bhagi-Damodaran

{"title":"Machine learning guided rational design of a non-heme iron-based lysine dioxygenase improves its total turnover number.","authors":"R Hunter Wilson, Daniel J Diaz, Anoop Rama Damodaran, Ambika Bhagi-Damodaran","doi":"10.1002/cbic.202400495","DOIUrl":"10.1002/cbic.202400495","url":null,"abstract":"Highly selective C-H functionalization remains an ongoing challenge in organic synthetic methodologies. Biocatalysts are robust tools for achieving these difficult chemical transformations. Biocatalyst engineering has often required directed evolution or structure-based rational design campaigns to improve their activities. In recent years, machine learning has been integrated into these workflows to improve the discovery of beneficial enzyme variants. In this work, we combine a structure-based machine-learning algorithm with classical molecular dynamics simulations to down select mutations for rational design of a non-heme iron-dependent lysine dioxygenase, LDO. This approach consistently resulted in functional LDO mutants and circumvents the need for extensive study of mutational activity before-hand. Our rationally designed single mutants purified with up to 2-fold higher yields than WT and displayed higher total turnover numbers (TTN). Combining five such single mutations into a pentamutant variant, LPNYI LDO, leads to a 40% improvement in the TTN (218±3) as compared to WT LDO (TTN = 160±2). Overall, this work offers a low-barrier approach for those seeking to synergize machine learning algorithms with pre-existing protein engineering strategies.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379640","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

Ligand-Induced Folding in a Dopamine-Binding DNA Aptamer. 配体诱导多巴胺结合 DNA 拟合体折叠。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-06 DOI: 10.1002/cbic.202400493

Yunus A Kaiyum, Emily Hoi Pui Chao, Lakshmi Dhar, Aron A Shoara, Minh-Dat Nguyen, Cameron D Mackereth, Philippe Dauphin-Ducharme, Philip E Johnson

{"title":"Ligand-Induced Folding in a Dopamine-Binding DNA Aptamer.","authors":"Yunus A Kaiyum, Emily Hoi Pui Chao, Lakshmi Dhar, Aron A Shoara, Minh-Dat Nguyen, Cameron D Mackereth, Philippe Dauphin-Ducharme, Philip E Johnson","doi":"10.1002/cbic.202400493","DOIUrl":"10.1002/cbic.202400493","url":null,"abstract":"Aptamers are often employed as molecular recognition elements in the development of different types of biosensors. Many of these biosensors take advantage of the aptamer having a ligand-induced structure-formation binding mechanism. However, this binding mechanism is poorly understood. Here we use isothermal titration calorimetry, circular dichroism spectroscopy and NMR spectroscopy to study the binding and ligand-induced structural change exhibited by a dopamine-binding DNA aptamer. We analysed a series of aptamers where we shorten the terminal stem that contains the 5' and 3' termini of the aptamer sequence. All aptamers bind dopamine in an enthalpically driven process coupled with an unfavorable entropy. A general trend of the aptamer having a weaker binding affinity is observed as the terminal stem is shortened. For all aptamers studied, numerous signals appear in the imino region of the 1H NMR spectrum indicating that new structure forms with ligand binding. However, it is only when this region of structure formation in the aptamer is brought close to the sensor surface that we obtain a functional electrochemical aptamer-based biosensor.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379639","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

Structural studies and functional validation of Eugenol and Ferulic acid against Enterococcus faecalis Sortase A. 丁香酚和阿魏酸对粪肠球菌分类酶 A 的结构研究和功能验证

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-06 DOI: 10.1002/cbic.202400554

Prashant Sharma, Akanksha Haldiya, Saumya Dubey, Himanshi Kain, Vijay Kumar Srivastava, Sandeep Kumar Srivastava, S L Kothari, Sanket Kaushik

{"title":"Structural studies and functional validation of Eugenol and Ferulic acid against Enterococcus faecalis Sortase A.","authors":"Prashant Sharma, Akanksha Haldiya, Saumya Dubey, Himanshi Kain, Vijay Kumar Srivastava, Sandeep Kumar Srivastava, S L Kothari, Sanket Kaushik","doi":"10.1002/cbic.202400554","DOIUrl":"https://doi.org/10.1002/cbic.202400554","url":null,"abstract":"Enterococcus faecalis (E. faecalis) is commonly occurring pathogen associated with nosocomial infections. Infections are difficult to treat because of their multidrug-resistant (MDR) nature and their tendency to form biofilms. Therefore, it is essential to find alternative medicinal approaches of treatment. In this regard, targeting an important protein for drug development can be an alternative approach. Sortase A (SrtA) is an important enzyme involved in anchoring cell surface-exposed proteins to the cell envelope. SrtA is present in Gram-positive bacteria which catalyses the attachment of several virulence factors and other proteins to the cell membrane. It is involved in bacterial pathogenesis, therefore, it's a promising drug target for the development of anti-microbial drugs targeting cell adhesion, evasion, and biofilm development. To identify SrtA potential inhibitors, we have purified E. faecalis Sortase A (EfSrtAΔN59). Structural studies along with molecular docking of protein with selected ligand molecules were done and confirmed by MD simulation experiments. We have also performed functional validation of these compounds on bacterial growth, anti-biofilm assays and inhibition assay of selected ligands were also done against E. faecalis individually and in synergistic combinations. Results indicated that both Eugenol and Ferulic acid bind to EfSrtAΔN59 with significant interactions and show promising results.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379642","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

Synthesis and Antimycobacterial Evaluation of Novel Pyrazole-Isoxazolines and Pyrazole-Isoxazoles. 新型吡唑-异噁唑类和吡唑-异噁唑类化合物的合成与抗霉菌评价。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-05 DOI: 10.1002/cbic.202400414

Paulo A Moraes, Thaise Dill Fussinger, Tuyla Fontana, Genilson S Pereira, Mário A Marangoni, Adriano F Camargo, Helio G Bonacorso, Marcos A P Martins, Alencar K Machado, Marli M A de Campos, Nilo Zanatta

{"title":"Synthesis and Antimycobacterial Evaluation of Novel Pyrazole-Isoxazolines and Pyrazole-Isoxazoles.","authors":"Paulo A Moraes, Thaise Dill Fussinger, Tuyla Fontana, Genilson S Pereira, Mário A Marangoni, Adriano F Camargo, Helio G Bonacorso, Marcos A P Martins, Alencar K Machado, Marli M A de Campos, Nilo Zanatta","doi":"10.1002/cbic.202400414","DOIUrl":"10.1002/cbic.202400414","url":null,"abstract":"This study reports the synthesis of a new series of pyrazole-isoxazolines, at very good yields, from the cyclocondensation reaction of pyrazole-enaminones with hydroxylamine hydrochloride. Dehydration of the pyrazole-isoxazolines furnished another new series of the respective pyrazole-isoxazoles, at excellent yields. Both series of the obtained compounds were screened for antimycobacterial activity, and compounds 4 f and 5 c showed significant inhibition of bacterial growth with a time- and concentration-dependent bactericidal effect. Cytotoxicity tests in VERO cell line did not indicate toxicity of compounds 4 f and 5 c regarding cellular prediction, NO production or dsDNA release. However, both compounds were associated with an increase in total ROS levels, providing induction of oxidative stress, but without compromising cellular targets. These results highlight compounds 4 f and 5 c as promising candidates for antimycobacterial treatment with a favorable safety profile.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378815","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

Precise Modulation of Protein Degradation by Smart PROTACs. 用智能 PROTACs 精确调节蛋白质降解。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-04 DOI: 10.1002/cbic.202400682

Junfei Cheng, Guoqiang Dong, Wei Wang, Chunquan Sheng

引用次数: 0

Effect of O-Acetylation on the Antigenicity and Glycoconjugate Immunogenicity of the Streptococcus Pneumoniae Serotype 7F Capsular Polysaccharide. O-acetylation 对肺炎链球菌血清型 7F 胶囊多糖抗原性和糖结合免疫原性的影响。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-04 DOI: 10.1002/cbic.202400684

Jean-Pierre Soubal, Aloyma Lugo, Darielys Santana-Mederos, Raine Garrido, Laura M Rodriguez-Noda, Rocmira Perez-Nicado, Yamilka Soroa-Millan, Mildrey Fariñas, Yury Valdés-Balbín, Dagmar García-Rivera, Daniel G Rivera, Vicente Vérez-Bencomo

{"title":"Effect of O-Acetylation on the Antigenicity and Glycoconjugate Immunogenicity of the Streptococcus Pneumoniae Serotype 7F Capsular Polysaccharide.","authors":"Jean-Pierre Soubal, Aloyma Lugo, Darielys Santana-Mederos, Raine Garrido, Laura M Rodriguez-Noda, Rocmira Perez-Nicado, Yamilka Soroa-Millan, Mildrey Fariñas, Yury Valdés-Balbín, Dagmar García-Rivera, Daniel G Rivera, Vicente Vérez-Bencomo","doi":"10.1002/cbic.202400684","DOIUrl":"10.1002/cbic.202400684","url":null,"abstract":"Streptococcus pneumoniae is a bacterial pathogen causing diseases as severe as pneumonia, sepsis and meningitis. Most commercial pneumococcal conjugate vaccines contain the 7F serotype, which is epidemiologically relevant and highly invasive. This serotype contains an O-acetyl group at the internal L-rhamnose of its polysaccharide repeating unit. Herein we report on the role of the O-acetyl moiety of 7F polysaccharide in both antigen recognition and the induction of a protective antibody response against 7F. Fully and partially de-O-acetylated 7F polysaccharides were chemically prepared and compared with the O-acetylated counterpart in their antigenicity and immunogenicity of their tetanus toxoid glycoconjugates. These comparative studies showed a slight but consistent decrease in the antigenicity for the fully de-O-acetylated polysaccharide, but not for the partly de-O-acetylated variant. The glycoconjugates derived from the O-acetylated and the fully de-O-acetylated polysaccharides had similar sizes and polysaccharide-to-protein ratio, and all proved both to be immunogenic and induce opsonophagocytic responses in mice. Nevertheless, the immune response elicited by the O-acetylated glycoconjugate was better in both quantity and quality, proving that the O-acetyl group is not strictly necessary but also not irrelevant for the antigenicity and immunogenicity of the 7F serotype polysaccharide and its glycoconjugates.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370364","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

Exploring DNA Computers: Advances in Storage, Cryptography and Logic Circuits. 探索 DNA 计算机：存储、密码学和逻辑电路方面的进展。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-04 DOI: 10.1002/cbic.202400670

Xiaolin Xie, Shuang Wang, Zhi Chen, Yifan Yu, Xiaoxue Hu, Ningning Ma, Min Ji, Ye Tian

引用次数: 0

Synthesis and Application of a Versatile Immunoproteasome Activity Probe. 多功能免疫蛋白酶体活性探针的合成与应用

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-04 DOI: 10.1002/cbic.202400571

Saayak Halder, Cody A Loy, Darci J Trader

引用次数: 0

Photoswitchable Detergents for Light-Controlled Liposome Lysis and Channel Gating. 用于光控脂质体裂解和通道门控的光开关洗涤剂。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-02 DOI: 10.1002/cbic.202400517

Max Löffler, David Repp, Fatime Beka, Ralph Wieneke

{"title":"Photoswitchable Detergents for Light-Controlled Liposome Lysis and Channel Gating.","authors":"Max Löffler, David Repp, Fatime Beka, Ralph Wieneke","doi":"10.1002/cbic.202400517","DOIUrl":"10.1002/cbic.202400517","url":null,"abstract":"Modulation of membrane properties via photoswitchable lipids has attracted attention due to the unparalleled spatiotemporal resolution of their functional control. Beside lipids, detergents are another prominent class for selective membrane perturbations owing to their ease of handling and spontaneous insertion in lipid bilayers. Herein, we describe the synthesis and characterization of three classes of visible light-sensitive surfactants with various azobenzene tail chain lengths. The photoswitchable detergents show water-solubility and micellization as well as undergo reversible isomerization under blue-/green light illumination. We demonstrate that the light-induced structural change of azobenzene can lead to vesicle rupture, making them a tool for controlled cargo release from vehicles. Via spontaneous insertion into the plasma membrane of mammalian cells transiently transfected with MscL, we used the azobenzene-derived detergents to optically activate the transmembrane mechanosensitive channel. This led to the rapid controlled uptake of membrane-impermeable molecules. Since detergents are extensively used in biochemistry and biotechnology, we propose that the photoswitchable detergents will be useful tools for the spatiotemporal modulation of membrane properties. Additionally, our work provides a design strategy for new detergents in membrane (protein) research.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360830","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