ACS Bio & Med Chem Au最新文献_第9页

IF 3.8

ACS Bio & Med Chem Au Pub Date : 2025-02-19

Xuewen Liu, Jing Chen, Hanxuan Wang, Benjamin Lambert and Ardemis A. Boghossian*,

引用次数: 0

IF 3.8

ACS Bio & Med Chem Au Pub Date : 2025-02-19

Tracy Yu, Arumay Biswas, Namita Dube and C. Denise Okafor*,

引用次数: 0

IF 3.8

ACS Bio & Med Chem Au Pub Date : 2025-02-19

Kang Lu, Yixian Wang, Chenhang Wang, Rui Liu, Kaiqiang Yang, Xuanchenye Zhang and Han Xiao*,

引用次数: 0

Chromatin Immunoprecipitation Reveals p53 Binding to G-Quadruplex DNA Sequences in Myeloid Leukemia Cell Lines 髓系白血病细胞系中染色质免疫沉淀揭示p53与g -四重体DNA序列的结合

IF 3.8

ACS Bio & Med Chem Au Pub Date : 2025-02-12 DOI: 10.1021/acsbiomedchemau.4c0012410.1021/acsbiomedchemau.4c00124

Libuše Kratochvilová, Alessandra Dinová, Natália Valková, Michaela Dobrovolná, Pedro A. Sánchez-Murcia and Václav Brázda*,

{"title":"Chromatin Immunoprecipitation Reveals p53 Binding to G-Quadruplex DNA Sequences in Myeloid Leukemia Cell Lines","authors":"Libuše Kratochvilová, Alessandra Dinová, Natália Valková, Michaela Dobrovolná, Pedro A. Sánchez-Murcia and Václav Brázda*, ","doi":"10.1021/acsbiomedchemau.4c0012410.1021/acsbiomedchemau.4c00124","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.4c00124https://doi.org/10.1021/acsbiomedchemau.4c00124","url":null,"abstract":"Clarifying functions of the p53 protein is a crucial aspect of cancer research. We analyzed the binding sites of p53 wild-type (WT) protein and its oncologically significant mutants and evaluated their transactivation properties using a functional yeast assay. Unlike the binding sites as determined in myeloid leukemia cell lines by chromatin immunoprecipitation of p53-R175H, p53-Y220C, p53-M237I, p53-R248Q, and p53-R273H mutants, the target sites of p53-WT and p53-R282W were significantly associated with putative G-quadruplex sequences (PQSs). Guanine-quadruplex (G-quadruplex or G4) formation in these sequences was evaluated by using a set of biophysical methods. G4s can modulate gene expression induced by p53. At low p53 expression level, PQS upstream of the p53-response element (RE) leads to greater gene expression induced by p53-R282W compared to that for the RE without PQS. Meanwhile, p53-WT protein expression is decreased by the PQS presence. At a high p53 expression level, the presence of PQS leads to a decreased expression of the reporter regardless of the distance and localization of the G4 from the RE.","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 2","pages":"283–298 283–298"},"PeriodicalIF":3.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsbiomedchemau.4c00124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143832764","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

Chromatin Immunoprecipitation Reveals p53 Binding to G-Quadruplex DNA Sequences in Myeloid Leukemia Cell Lines. 髓系白血病细胞系中染色质免疫沉淀揭示p53与g -四重体DNA序列的结合。

IF 3.8

ACS Bio & Med Chem Au Pub Date : 2025-02-12 eCollection Date: 2025-04-16 DOI: 10.1021/acsbiomedchemau.4c00124

Libuše Kratochvilová, Alessandra Dinová, Natália Valková, Michaela Dobrovolná, Pedro A Sánchez-Murcia, Václav Brázda

{"title":"Chromatin Immunoprecipitation Reveals p53 Binding to G-Quadruplex DNA Sequences in Myeloid Leukemia Cell Lines.","authors":"Libuše Kratochvilová, Alessandra Dinová, Natália Valková, Michaela Dobrovolná, Pedro A Sánchez-Murcia, Václav Brázda","doi":"10.1021/acsbiomedchemau.4c00124","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.4c00124","url":null,"abstract":"Clarifying functions of the p53 protein is a crucial aspect of cancer research. We analyzed the binding sites of p53 wild-type (WT) protein and its oncologically significant mutants and evaluated their transactivation properties using a functional yeast assay. Unlike the binding sites as determined in myeloid leukemia cell lines by chromatin immunoprecipitation of p53-R175H, p53-Y220C, p53-M237I, p53-R248Q, and p53-R273H mutants, the target sites of p53-WT and p53-R282W were significantly associated with putative G-quadruplex sequences (PQSs). Guanine-quadruplex (G-quadruplex or G4) formation in these sequences was evaluated by using a set of biophysical methods. G4s can modulate gene expression induced by p53. At low p53 expression level, PQS upstream of the p53-response element (RE) leads to greater gene expression induced by p53-R282W compared to that for the RE without PQS. Meanwhile, p53-WT protein expression is decreased by the PQS presence. At a high p53 expression level, the presence of PQS leads to a decreased expression of the reporter regardless of the distance and localization of the G4 from the RE.","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 2","pages":"283-298"},"PeriodicalIF":3.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054037","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 Reverse Transcription Nucleic-Acid-Based Barcoding System for In Vivo Measurement of Lipid Nanoparticle mRNA Delivery 一个基于反转录核酸的条形码系统在体内测量脂质纳米颗粒mRNA传递

IF 3.8

ACS Bio & Med Chem Au Pub Date : 2025-02-05 DOI: 10.1021/acsbiomedchemau.4c0008110.1021/acsbiomedchemau.4c00081

Kevin C. Wang, Tiana L. Young, Jingan Chen, Shannon N. Tsai, Yue Xu, Andrew J. Varley, Nicholas C. Solek, Fanglin Gong, Rick X. Z. Lu, Basil P. Hubbard and Bowen Li*,

{"title":"A Reverse Transcription Nucleic-Acid-Based Barcoding System for In Vivo Measurement of Lipid Nanoparticle mRNA Delivery","authors":"Kevin C. Wang, Tiana L. Young, Jingan Chen, Shannon N. Tsai, Yue Xu, Andrew J. Varley, Nicholas C. Solek, Fanglin Gong, Rick X. Z. Lu, Basil P. Hubbard and Bowen Li*, ","doi":"10.1021/acsbiomedchemau.4c0008110.1021/acsbiomedchemau.4c00081","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.4c00081https://doi.org/10.1021/acsbiomedchemau.4c00081","url":null,"abstract":"Lipid nanoparticles (LNPs) are the most extensively validated clinical delivery vehicles for mRNA therapeutics, exemplified by their widespread use in the mRNA COVID-19 vaccines. The pace of lipid nanoparticle (LNP) development for mRNA therapeutics is restricted by the limitations of existing methods for large-scale LNP screening. To address this challenge, we developed Quantitative Analysis of Reverse Transcribed Barcodes (QuART), a novel nucleic-acid-based system for measuring LNP functional delivery in vivo. QuART uses a bacterial retron reverse transcription system to couple functional mRNA delivery into the cytoplasm with a cDNA barcode readout. Our results demonstrate that QuART can be used to identify functional mRNA delivery both in vitro in cell culture and in vivo in mice. Multiplexing of QuART could enable high-throughput screening of LNP formulations, facilitating the rapid discovery of promising LNP candidates for mRNA therapeutics.","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 1","pages":"35–41 35–41"},"PeriodicalIF":3.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsbiomedchemau.4c00081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436346","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 Reverse Transcription Nucleic-Acid-Based Barcoding System for In Vivo Measurement of Lipid Nanoparticle mRNA Delivery. 一个基于反转录核酸的条形码系统在体内测量脂质纳米颗粒mRNA传递。

IF 3.8

ACS Bio & Med Chem Au Pub Date : 2025-02-05 eCollection Date: 2025-02-19 DOI: 10.1021/acsbiomedchemau.4c00081

Kevin C Wang, Tiana L Young, Jingan Chen, Shannon N Tsai, Yue Xu, Andrew J Varley, Nicholas C Solek, Fanglin Gong, Rick X Z Lu, Basil P Hubbard, Bowen Li

{"title":"A Reverse Transcription Nucleic-Acid-Based Barcoding System for In Vivo Measurement of Lipid Nanoparticle mRNA Delivery.","authors":"Kevin C Wang, Tiana L Young, Jingan Chen, Shannon N Tsai, Yue Xu, Andrew J Varley, Nicholas C Solek, Fanglin Gong, Rick X Z Lu, Basil P Hubbard, Bowen Li","doi":"10.1021/acsbiomedchemau.4c00081","DOIUrl":"10.1021/acsbiomedchemau.4c00081","url":null,"abstract":"Lipid nanoparticles (LNPs) are the most extensively validated clinical delivery vehicles for mRNA therapeutics, exemplified by their widespread use in the mRNA COVID-19 vaccines. The pace of lipid nanoparticle (LNP) development for mRNA therapeutics is restricted by the limitations of existing methods for large-scale LNP screening. To address this challenge, we developed Quantitative Analysis of Reverse Transcribed Barcodes (QuART), a novel nucleic-acid-based system for measuring LNP functional delivery in vivo. QuART uses a bacterial retron reverse transcription system to couple functional mRNA delivery into the cytoplasm with a cDNA barcode readout. Our results demonstrate that QuART can be used to identify functional mRNA delivery both in vitro in cell culture and in vivo in mice. Multiplexing of QuART could enable high-throughput screening of LNP formulations, facilitating the rapid discovery of promising LNP candidates for mRNA therapeutics.","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 1","pages":"35-41"},"PeriodicalIF":3.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484059","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

Antimicrobial Efficacy of 1,2,3-Triazole-Incorporated Indole-Pyrazolone against Drug-Resistant ESKAPE Pathogens: Design and Synthesis. 1,2,3-三唑-吲哚吡唑酮对耐药ESKAPE病原菌的抗菌效果：设计与合成。

IF 3.8

ACS Bio & Med Chem Au Pub Date : 2025-01-28 eCollection Date: 2025-02-19 DOI: 10.1021/acsbiomedchemau.4c00060

Dipti B Upadhyay, Jaydeep A Mokariya, Paras J Patel, Subham G Patel, Mehul P Parmar, Disha P Vala, Febe Ferro, Dhanji P Rajani, Mahesh Narayan, Jyotish Kumar, Sourav Banerjee, Hitendra M Patel

{"title":"Antimicrobial Efficacy of 1,2,3-Triazole-Incorporated Indole-Pyrazolone against Drug-Resistant ESKAPE Pathogens: Design and Synthesis.","authors":"Dipti B Upadhyay, Jaydeep A Mokariya, Paras J Patel, Subham G Patel, Mehul P Parmar, Disha P Vala, Febe Ferro, Dhanji P Rajani, Mahesh Narayan, Jyotish Kumar, Sourav Banerjee, Hitendra M Patel","doi":"10.1021/acsbiomedchemau.4c00060","DOIUrl":"10.1021/acsbiomedchemau.4c00060","url":null,"abstract":"In the current study, we report the synthesis of novel 4-((1-((1H-1,2,3-triazole-4-yl)methyl)-1H-indol-3-yl)methylene)-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazole-3-one derivatives 5a-o. The compounds were prepared through a Knoevenagel condensation reaction and copper-catalyzed azide-alkyne cycloaddition (CuAAC) Click chemistry approach. The synthesized compounds exhibited promising antimicrobial activity against both Gram-positive and Gram-negative bacteria. Compounds 5e, 5h, and 5i displayed potent activity with MIC value 10 μg/mL against Acinetobacter baumannii, in comparison to standard drugs chloramphenicol and ampicillin. Compounds 5d, 5h, 5i, 5l, 5m, and 5n exhibited good-to-moderate antifungal activity against Candida albicans and Aspergillus niger equivalent to standard drugs nystatin and fluconazole. In this study, the cytotoxicity profile of a series of compounds was assessed using SHSY-5Y cells. The results indicate that compounds 5a-o exhibit no significant cytotoxicity at concentrations up to 100 μg/mL, in comparison to both untreated and vehicle control groups. These findings highlight the safety and tolerability of compounds as well as the potential of the synthesized compounds as effective agents against bacterial and fungal infections.","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 1","pages":"66-77"},"PeriodicalIF":3.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484043","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

Antimicrobial Efficacy of 1,2,3-Triazole-Incorporated Indole-Pyrazolone against Drug-Resistant ESKAPE Pathogens: Design and Synthesis 1,2,3-三唑-吲哚吡唑酮对耐药ESKAPE病原菌的抗菌效果：设计与合成

IF 3.8

ACS Bio & Med Chem Au Pub Date : 2025-01-28 DOI: 10.1021/acsbiomedchemau.4c0006010.1021/acsbiomedchemau.4c00060

Dipti B. Upadhyay, Jaydeep A. Mokariya, Paras J. Patel, Subham G. Patel, Mehul P. Parmar, Disha P. Vala, Febe Ferro, Dhanji P. Rajani, Mahesh Narayan, Jyotish Kumar, Sourav Banerjee* and Hitendra M. Patel*,

{"title":"Antimicrobial Efficacy of 1,2,3-Triazole-Incorporated Indole-Pyrazolone against Drug-Resistant ESKAPE Pathogens: Design and Synthesis","authors":"Dipti B. Upadhyay, Jaydeep A. Mokariya, Paras J. Patel, Subham G. Patel, Mehul P. Parmar, Disha P. Vala, Febe Ferro, Dhanji P. Rajani, Mahesh Narayan, Jyotish Kumar, Sourav Banerjee* and Hitendra M. Patel*, ","doi":"10.1021/acsbiomedchemau.4c0006010.1021/acsbiomedchemau.4c00060","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.4c00060https://doi.org/10.1021/acsbiomedchemau.4c00060","url":null,"abstract":"In the current study, we report the synthesis of novel 4-((1-((1H-1,2,3-triazole-4-yl)methyl)-1H-indol-3-yl)methylene)-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazole-3-one derivatives 5a–o. The compounds were prepared through a Knoevenagel condensation reaction and copper-catalyzed azide–alkyne cycloaddition (CuAAC) Click chemistry approach. The synthesized compounds exhibited promising antimicrobial activity against both Gram-positive and Gram-negative bacteria. Compounds 5e, 5h, and 5i displayed potent activity with MIC value 10 μg/mL against Acinetobacter baumannii, in comparison to standard drugs chloramphenicol and ampicillin. Compounds 5d, 5h, 5i, 5l, 5m, and 5n exhibited good-to-moderate antifungal activity against Candida albicans and Aspergillus niger equivalent to standard drugs nystatin and fluconazole. In this study, the cytotoxicity profile of a series of compounds was assessed using SHSY-5Y cells. The results indicate that compounds 5a–o exhibit no significant cytotoxicity at concentrations up to 100 μg/mL, in comparison to both untreated and vehicle control groups. These findings highlight the safety and tolerability of compounds as well as the potential of the synthesized compounds as effective agents against bacterial and fungal infections.","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 1","pages":"66–77 66–77"},"PeriodicalIF":3.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsbiomedchemau.4c00060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436040","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

Cation Pretreatment Enables the Saline Stability of a Near-Infrared Sensor for Dopamine. 阳离子预处理使多巴胺近红外传感器在生理盐水中的稳定性得以实现。

IF 3.8

ACS Bio & Med Chem Au Pub Date : 2025-01-27 eCollection Date: 2025-02-19 DOI: 10.1021/acsbiomedchemau.4c00094

Xuewen Liu, Jing Chen, Hanxuan Wang, Benjamin Lambert, Ardemis A Boghossian

{"title":"Cation Pretreatment Enables the Saline Stability of a Near-Infrared Sensor for Dopamine.","authors":"Xuewen Liu, Jing Chen, Hanxuan Wang, Benjamin Lambert, Ardemis A Boghossian","doi":"10.1021/acsbiomedchemau.4c00094","DOIUrl":"10.1021/acsbiomedchemau.4c00094","url":null,"abstract":"Single-walled carbon nanotubes (SWCNTs) are wrapped with single-stranded DNA (ssDNA) to create near-infrared (NIR-II) fluorescent sensors for diverse analytes. However, the interaction between the negatively charged backbone of ssDNA and cations in biological saline alters fluorescence unpredictably. This susceptibility limits the application of these sensors in biological media. To address this limitation, this study develops a cation-pretreatment strategy that quenches the baseline fluorescence of ssDNA-SWCNTs to enable turn-on responses that are selectively triggered by analytes in saline. An initial screening of Na+, K+, Mg2+, Ca2+, and Al3+ pretreatments of gel-encapsulated (AT)15-SWCNTs reveals that Al3+ pretreatment induces a stable quenching of fluorescence that is reversible only on Al3+ chelation or precipitation. We apply this Al3+ pretreatment to develop a saline-resilient, near-infrared sensor for dopamine. The Al3+-treated (AT)15-SWCNTs show a concentration- and chirality-dependent fluorescence response over a dynamic range of 1 nM and 10 μM dopamine, achieving a 110-fold increase in the turn-on response to 10 mM dopamine in buffered saline compared with the untreated (AT)15-SWCNTs. Further study of the effects of pH and different salts on the dopamine response suggests a mechanism that relies on competing trivalent cations and negative DNA phosphate interactions. These interactions lay the framework for saline-resilient optical sensors that exploit DNA as a charged-based actuator for modulating the exciton dynamics and controlling the SWCNT fluorescence.","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 1","pages":"166-174"},"PeriodicalIF":3.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484050","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