ACS Chemical Biology最新文献_第8页

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-07-18

Hyun Bong Park, Deguang Song, Mytien Nguyen, Noah W. Palm* and Jason M. Crawford*,

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IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-07-18

Ram J. Tharu, Emmett Hanson and Mehmet V. Yigit*,

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IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-07-18

Panayotis C. Theodoropoulos, Holly H. Guo, Wentian Wang, Eric Crossley, Giomar Rivera Cancel, Min Fang, Thu Nguyen, Hamid Baniasadi, Noelle S. Williams, Joseph M. Ready, Jef K. De Brabander* and Deepak Nijhawan*,

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IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-07-18

Juho Alaviuhkola, Sondos Abdulmajeed, Sven T. Sowa, Johan Pääkkönen and Lari Lehtiö*,

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IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-07-18

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IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-07-18

Xinlong Guo, Xuelian Ren, Cong Yan and He Huang*,

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Live-Cell NanoBRET Assay to Measure AKT Inhibitor Binding to Conformational States of AKT. 活细胞NanoBRET测定AKT抑制剂与AKT构象状态的结合。

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-07-18 Epub Date: 2025-07-09 DOI: 10.1021/acschembio.5c00213

Jeremy W Harris, Flávio Antônio de Oliveira Simões, Erin N Ryerson, William M Marsiglia

{"title":"Live-Cell NanoBRET Assay to Measure AKT Inhibitor Binding to Conformational States of AKT.","authors":"Jeremy W Harris, Flávio Antônio de Oliveira Simões, Erin N Ryerson, William M Marsiglia","doi":"10.1021/acschembio.5c00213","DOIUrl":"10.1021/acschembio.5c00213","url":null,"abstract":"AKT is the main protein kinase of the PI3K-AKT pathway, interacting with over one hundred protein partners to facilitate cellular processes that allow cancer cells to survive and proliferate. It is an attractive target due to its control over many cellular outputs. However, ATP-competitive and allosteric AKT inhibitors have performed poorly in clinical trials. AKT inhibitor interactions with AKT are multifaceted and influence the catalytic activity of AKT, its conformation, its ability to interact with binding partners, and its phosphorylation state. Therefore, a better understanding of how these inhibitors influence these parameters is needed, especially in a cellular context. Using a live-cell NanoBRET target engagement assay to query the binding of AKT inhibitors to all isoforms of AKT, we found that ATP-competitive inhibitors bind similarly across all three isoforms and allosteric inhibitors bind more heterogeneously. Further, assaying gain-of-function pathological mutants and myristoylated active versions of all AKT isoforms revealed that T308 phosphorylation enhances the binding of ATP-competitive inhibitors. We found that this phosphorylation is a good indicator of cell viability sensitivity to ATP-competitive inhibitors when comparing effects on known resistant and sensitive triple-negative breast cancer cell lines. Taken together, these findings are useful for screening new AKT inhibitors, and these findings represent important considerations in developing the next generation of AKT inhibitors.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"1635-1645"},"PeriodicalIF":3.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","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 Endoplasmic Reticulum-Located TRPV1 Channel Is Not Thermal Sensitive. 位于内质网的TRPV1通道不热敏。

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-07-17 DOI: 10.1021/acschembio.5c00306

Elena O Petukhova, Dmitry I Maltsev, Daria Y Pechinko, Andrei L Kalinichenko, Vsevolod V Belousov, Oleg V Podgorny

{"title":"The Endoplasmic Reticulum-Located TRPV1 Channel Is Not Thermal Sensitive.","authors":"Elena O Petukhova, Dmitry I Maltsev, Daria Y Pechinko, Andrei L Kalinichenko, Vsevolod V Belousov, Oleg V Podgorny","doi":"10.1021/acschembio.5c00306","DOIUrl":"https://doi.org/10.1021/acschembio.5c00306","url":null,"abstract":"Transient receptor potential vanilloid subfamily member 1 (TRPV1), also known as the capsaicin receptor, plays a central role in detecting noxious heat, regulating thermal homeostasis, and mediating inflammatory responses. TRPV1 is a cell membrane-associated, nonselective cation channel. TRPV1 activation triggers transmembrane depolarizing currents and elevates the level of cytosolic calcium. A large fraction of TRPV1 is known to reside in the endoplasmic reticulum (ER), and ligand-dependent activation of this fraction elicits calcium release from the ER. However, whether ER-located TRPV1 participates in the heat-evoked cytosolic calcium elevation remains unresolved. In this study, we heterologously expressed human TRPV1 in HEK293TN cells, which do not normally exhibit physiological responses to temperature variations, and recorded calcium changes in response to heat stimulation and capsaicin treatment in the presence of extracellular calcium and after its removal. Our experiments revealed that heat-evoked calcium responses were abolished in hTRPV1-expressing HEK293TN cells upon removal of extracellular calcium, whereas the TRPV1 agonist capsaicin still elicited an elevation of intracellular calcium. The restoration of extracellular calcium after its withdrawal recovered heat-evoked calcium responses. Our findings argue for differential sensitivity of TRPV1 pools (ER vs plasma membrane) for discriminating various physiological and noxious signals and may allow for elucidating the structural basis of temperature-dependent gating.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Pair of DNA Aptamers That Can Selectively Bind to Bilirubin and Biliverdin. 一对能选择性结合胆红素和胆绿素的DNA适体。

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-07-16 DOI: 10.1021/acschembio.5c00438

Yachen Xie, Yunus A Kaiyum, Lide Gu, Yibo Liu, Philip E Johnson, Juewen Liu

{"title":"A Pair of DNA Aptamers That Can Selectively Bind to Bilirubin and Biliverdin.","authors":"Yachen Xie, Yunus A Kaiyum, Lide Gu, Yibo Liu, Philip E Johnson, Juewen Liu","doi":"10.1021/acschembio.5c00438","DOIUrl":"https://doi.org/10.1021/acschembio.5c00438","url":null,"abstract":"Bilirubin and biliverdin are two important metabolites from the degradation of heme. Development of aptamers for them will not only help with the measurement of their concentrations for diagnosing diseases such as neonatal jaundice and liver dysfunction, but may also aid in developing molecular switches for the regulation of gene expression. In this work, we report the selection of DNA aptamers against bilirubin and biliverdin. For the biliverdin selection, the tightest affinity aptamer has a dissociation costant (Kd) value of 6 nM determined using isothermal titration calorimetry (ITC), and using a fluorescent strand-displacement assay, a limit of detection of 0.7 nM was achieved. This strand-displacement sensor also showed a response to bilirubin, although with a 10-fold lower affinity. For the bilirubin selection, many sequences obtained were also present in the biliverdin selection, and it was attributed to the oxidation of a fraction of bilirubin to biliverdin by air. This oxidation was confirmed by a visual color change of bilirubin and by UV-vis spectroscopy. The tightest binding bilirubin aptamer has a Kd value of 203 nM based on ITC, and a detection limit of 47 nM was achieved using the strand-displacement assay. This pair of aptamers offer insights into molecular recognition of heme breakdown products and may be useful for developing biosensors and intracellular molecular switches.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Inverted Molecular Beacons as Reaction-Based Hybridization Probes for Small-Molecule Activation by Nucleic Acid Inputs. 倒置分子信标作为基于反应的杂交探针用于核酸输入激活小分子。

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-07-15 DOI: 10.1021/acschembio.5c00333

Cole Emanuelson, Anirban Bardhan, Nicholas Ankenbruck, Jessica Boette, Alexander Deiters

{"title":"Inverted Molecular Beacons as Reaction-Based Hybridization Probes for Small-Molecule Activation by Nucleic Acid Inputs.","authors":"Cole Emanuelson, Anirban Bardhan, Nicholas Ankenbruck, Jessica Boette, Alexander Deiters","doi":"10.1021/acschembio.5c00333","DOIUrl":"https://doi.org/10.1021/acschembio.5c00333","url":null,"abstract":"Nucleic acid-based hybridization probes that produce a fluorescent signal in the presence of DNA or RNA target molecules are essential components of nucleic acid computation and detection strategies. Commonly, the fluorescence activation of reporter gates is triggered by separation of a fluorophore-quencher pair upon target hybridization or strand displacement. In order to expand the utility of DNA computing by providing a chemical reaction as the ultimate output, reporter systems have been designed that carry reactive groups, which undergo a proximity-induced reaction upon oligonucleotide hybridization. The downside of published reporter gate designs is that they are composed of two separate, chemically modified oligonucleotides, which need to be taken into consideration when designing upstream circuits. Here, we report a novel hairpin-forming nucleic acid reporter probe that utilizes template-induced proximal reactivity to activate a small molecule in the presence of an unmodified nucleic acid input molecule. This DNA hairpin reporter gate consists of a duplex between a blocking strand and a hairpin-forming reporter strand. In the presence of input, the blocking strand is displaced, triggering hairpin formation allowing the proximity-driven templated activation of a vinyl ether-caged fluorophore by a tetrazine via an inverse electron demand Diels-Alder reaction. This new approach demonstrates robust small-molecule activation in vitro and in cells through logic operations in the presence of input DNA molecules.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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