ACS Central Science最新文献

筛选
英文 中文
A New Facility Will Harness Plasma to Guide Interplanetary Craft 利用等离子体引导星际飞船的新设施
IF 18.2 1区 化学
ACS Central Science Pub Date : 2024-07-10 DOI: 10.1021/acscentsci.4c01052
Katherine Bourzac
{"title":"A New Facility Will Harness Plasma to Guide Interplanetary Craft","authors":"Katherine Bourzac","doi":"10.1021/acscentsci.4c01052","DOIUrl":"https://doi.org/10.1021/acscentsci.4c01052","url":null,"abstract":"A plasma wind tunnel being built in Colorado will help test new ideas about navigating hypersonic vehicles in harsh conditions.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141587121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Semisynthetic Oligomannuronic Acid-Based Glycoconjugate Vaccine against Pseudomonas aeruginosa 基于半合成寡甘露糖酸的铜绿假单胞菌糖结合疫苗
IF 18.2 1区 化学
ACS Central Science Pub Date : 2024-07-09 DOI: 10.1021/acscentsci.4c00387
Yiyue Zhang, Xiaotong Wang, Youling Liang, Liangliang Zhang, Jiahao Fan, You Yang
{"title":"A Semisynthetic Oligomannuronic Acid-Based Glycoconjugate Vaccine against Pseudomonas aeruginosa","authors":"Yiyue Zhang, Xiaotong Wang, Youling Liang, Liangliang Zhang, Jiahao Fan, You Yang","doi":"10.1021/acscentsci.4c00387","DOIUrl":"https://doi.org/10.1021/acscentsci.4c00387","url":null,"abstract":"<i>Pseudomonas aeruginosa</i> is one of the leading causes of nosocomial infections and has become increasingly resistant to multiple antibiotics. However, development of novel classes of antibacterial agents against multidrug-resistant <i>P. aeruginosa</i> is extremely difficult. Herein we develop a semisynthetic oligomannuronic acid-based glycoconjugate vaccine that confers broad protection against infections of both mucoid and nonmucoid strains of <i>P. aeruginosa</i>. The well-defined glycoconjugate vaccine formulated with Freund’s adjuvant (FA) employing a highly conserved antigen elicited a strong and specific immune response and protected mice against both mucoid and nonmucoid strains of <i>P. aeruginosa</i>. The resulting antibodies recognized different strains of <i>P. aeruginosa</i> and mediated the opsonic killing of the bacteria at varied levels depending on the amount of alginate expressed on the surface of the strains. Vaccination with the glycoconjugate vaccine plus FA significantly promoted the pulmonary and blood clearance of the mucoid PAC1 strain of <i>P. aeruginosa</i> and considerably improved the survival rates of mice against the nonmucoid PAO1 strain of <i>P. aeruginosa</i>. Thus, the semisynthetic glycoconjugate is a promising vaccine that may provide broad protection against both types of <i>P. aeruginosa</i>.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141587265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spatial Visualization of A-to-I Editing in Cells Using Endonuclease V Immunostaining Assay (EndoVIA) 利用内切酶 V 免疫染色测定 (EndoVIA) 观察细胞中 A 到 I 编辑的空间可视化情况
IF 18.2 1区 化学
ACS Central Science Pub Date : 2024-07-07 DOI: 10.1021/acscentsci.4c00444
Alexandria L. Quillin, Benoît Arnould, Steve D. Knutson, Jennifer M. Heemstra
{"title":"Spatial Visualization of A-to-I Editing in Cells Using Endonuclease V Immunostaining Assay (EndoVIA)","authors":"Alexandria L. Quillin, Benoît Arnould, Steve D. Knutson, Jennifer M. Heemstra","doi":"10.1021/acscentsci.4c00444","DOIUrl":"https://doi.org/10.1021/acscentsci.4c00444","url":null,"abstract":"Adenosine-to-inosine (A-to-I) editing is one of the most widespread post-transcriptional RNA modifications and is catalyzed by adenosine deaminases acting on RNA (ADARs). Varying across tissue types, A-to-I editing is essential for numerous biological functions, and dysregulation leads to autoimmune and neurological disorders, as well as cancer. Recent evidence has also revealed a link between RNA localization and A-to-I editing, yet understanding of the mechanisms underlying this relationship and its biological impact remains limited. Current methods rely primarily on <i>in vitro</i> characterization of extracted RNA that ultimately erases subcellular localization and cell-to-cell heterogeneity. To address these challenges, we have repurposed endonuclease V (EndoV), a magnesium-dependent ribonuclease that cleaves inosine bases in edited RNA, to selectively bind and detect A-to-I edited RNA in cells. The work herein introduces an endonuclease V immunostaining assay (EndoVIA), a workflow that provides spatial visualization of edited transcripts, enables rapid quantification of overall inosine abundance, and maps the landscape of A-to-I editing within the transcriptome at the nanoscopic level.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141574769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Novel Prodrug Strategy Based on Reversibly Degradable Guanidine Imides for High Oral Bioavailability and Prolonged Pharmacokinetics of Broad-Spectrum Anti-influenza Agents 一种基于可逆降解胍酰亚胺的新型原药策略,用于提高广谱抗流感药物的口服生物利用度和延长药代动力学时间
IF 18.2 1区 化学
ACS Central Science Pub Date : 2024-07-04 DOI: 10.1021/acscentsci.4c00548
Yujeong Jung, Soo Bin Ahn, Taeyang An, Hyeon-Min Cha, Minjae Kim, Hyunjin Cheon, Yejin Jang, Haemi Lee, Byungil Kim, Meehyein Kim, Yan Lee
{"title":"A Novel Prodrug Strategy Based on Reversibly Degradable Guanidine Imides for High Oral Bioavailability and Prolonged Pharmacokinetics of Broad-Spectrum Anti-influenza Agents","authors":"Yujeong Jung, Soo Bin Ahn, Taeyang An, Hyeon-Min Cha, Minjae Kim, Hyunjin Cheon, Yejin Jang, Haemi Lee, Byungil Kim, Meehyein Kim, Yan Lee","doi":"10.1021/acscentsci.4c00548","DOIUrl":"https://doi.org/10.1021/acscentsci.4c00548","url":null,"abstract":"We present orally administrable prodrugs (<b>OSC-GCDI</b>s) of guanidino oseltamivir carboxylate (<b>GOC</b>) based on guanidine cyclic diimide (GCDI) to treat influenza viruses. By concealing the guanidine group, which significantly limits the intestinal absorption, its prodrugs <b>OSC-GCDI</b>s demonstrate dramatic improvement of oral bioavailability. The most promising antiviral substance <b>OSC-GCDI(P)</b> readily forms covalent adducts with serum proteins via a degradable linker after the intestinal absorption. Subsequently, the active species, <b>GOC</b>, is released from the conjugate in a sustained manner, which greatly contributes to improving pharmacokinetic properties. Because of the remarkable improvements in both oral bioavailability and longevity of its active metabolite, <b>OSC-GCDI(P)</b> demonstrates outstanding therapeutic efficacy against both wild-type and oseltamivir-resistant (H275Y) influenza virus strains in a mouse infection model, even with a single oral administration.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141549866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cryo-tomography and 3D Electron Diffraction Reveal the Polar Habit and Chiral Structure of the Malaria Pigment Crystal Hemozoin 低温层析技术和三维电子衍射揭示疟疾色素晶体 Hemozoin 的极性习性和手性结构
IF 18.2 1区 化学
ACS Central Science Pub Date : 2024-07-04 DOI: 10.1021/acscentsci.4c00162
Paul Benjamin Klar, David Geoffrey Waterman, Tim Gruene, Debakshi Mullick, Yun Song, James Boris Gilchrist, C. David Owen, Wen Wen, Idan Biran, Lothar Houben, Neta Regev-Rudzki, Ron Dzikowski, Noa Marom, Lukas Palatinus, Peijun Zhang, Leslie Leiserowitz, Michael Elbaum
{"title":"Cryo-tomography and 3D Electron Diffraction Reveal the Polar Habit and Chiral Structure of the Malaria Pigment Crystal Hemozoin","authors":"Paul Benjamin Klar, David Geoffrey Waterman, Tim Gruene, Debakshi Mullick, Yun Song, James Boris Gilchrist, C. David Owen, Wen Wen, Idan Biran, Lothar Houben, Neta Regev-Rudzki, Ron Dzikowski, Noa Marom, Lukas Palatinus, Peijun Zhang, Leslie Leiserowitz, Michael Elbaum","doi":"10.1021/acscentsci.4c00162","DOIUrl":"https://doi.org/10.1021/acscentsci.4c00162","url":null,"abstract":"Detoxification of heme in <i>Plasmodium</i> depends on its crystallization into hemozoin. This pathway is a major target of antimalarial drugs. The crystalline structure of hemozoin was established by X-ray powder diffraction using a synthetic analog, β-hematin. Here, we apply emerging methods of <i>in situ</i> cryo-electron tomography and 3D electron diffraction to obtain a definitive structure of hemozoin directly from ruptured parasite cells. Biogenic hemozoin crystals take a striking polar morphology. Like β-hematin, the unit cell contains a heme dimer, which may form four distinct stereoisomers: two centrosymmetric and two chiral enantiomers. Diffraction analysis, supported by density functional theory analysis, reveals a selective mixture in the hemozoin lattice of one centrosymmetric and one chiral dimer. Absolute configuration has been determined by morphological analysis and confirmed by a novel method of exit-wave reconstruction from a focal series. Atomic disorder appears on specific facets asymmetrically, and the polar morphology can be understood in light of water binding. Structural modeling of the heme detoxification protein suggests a function as a chiral agent to bias the dimer formation in favor of rapid growth of a single crystalline phase. The refined structure of hemozoin should serve as a guide to new drug development.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141549865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Conversation with Rob Jackson 对话罗布-杰克逊
IF 18.2 1区 化学
ACS Central Science Pub Date : 2024-07-01 DOI: 10.1021/acscentsci.4c01007
Katherine Bourzac
{"title":"A Conversation with Rob Jackson","authors":"Katherine Bourzac","doi":"10.1021/acscentsci.4c01007","DOIUrl":"https://doi.org/10.1021/acscentsci.4c01007","url":null,"abstract":"In his new book, the climate scientist lays out the case for restoring the atmosphere.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141549868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to “A Multiscale Study of Phosphorylcholine Driven Cellular Phenotypic Targeting” 对 "磷酰胆碱驱动的细胞表型靶向的多尺度研究 "的更正
IF 18.2 1区 化学
ACS Central Science Pub Date : 2024-07-01 DOI: 10.1021/acscentsci.4c00878
Silvia Acosta-Gutiérrez, Diana Matias, Milagros Avila-Olias, Virginia M. Gouveia, Edoardo Scarpa, Joe Forth, Claudia Contini, Aroa Duro-Castano, Loris Rizzello, Giuseppe Battaglia
{"title":"Correction to “A Multiscale Study of Phosphorylcholine Driven Cellular Phenotypic Targeting”","authors":"Silvia Acosta-Gutiérrez, Diana Matias, Milagros Avila-Olias, Virginia M. Gouveia, Edoardo Scarpa, Joe Forth, Claudia Contini, Aroa Duro-Castano, Loris Rizzello, Giuseppe Battaglia","doi":"10.1021/acscentsci.4c00878","DOIUrl":"https://doi.org/10.1021/acscentsci.4c00878","url":null,"abstract":"The Acknowledgment section should include the phrase: “SAG acknowledges support from an AGAUR Beatriu de Pinós MSCA-COFUND Fellowship (project 2020-BP-00177).” The full, revised Acknowledgment section is included below. We would like to thank Dr I. Canton for useful discussion at the early stages of the work that helped to identify the receptors. SAG acknowledges support from an AGAUR Beatriu de Pinós MSCA-COFUND Fellowship (project 2020-BP-00177). We thank the Children with Cancer UK (16-227) for SAG and ES salaries, the EPSRC (EP/R024723/1) for DM salaries, the ERC (CheSSTaG 769798) for JF and part of GB salary, the EPSRC (EP/G062137/1) for JM salary. MAO thanks the BBSRC doctoral training grant Sheffield for her PhD studentship. JG thanks the DFG for sponsoring his fellowship. VMG thanks the received financial support from Fundação para a Ciência e Tencnologia (PD/BD/128388/2017). ADC and LR thank the Marie Skłodowska Curie program for sponsoring their fellowship. GB thanks the EPSRC (EP/N026322/1) for his personal fellowship. This article has not yet been cited by other publications.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141549867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nonidealities in CO2 Electroreduction Mechanisms Revealed by Automation-Assisted Kinetic Analysis 自动化辅助动力学分析揭示二氧化碳电还原机制的非理想性
IF 18.2 1区 化学
ACS Central Science Pub Date : 2024-06-28 DOI: 10.1021/acscentsci.3c01295
Joy S. Zeng, Vineet Padia, Grace Y. Chen, Joseph H. Maalouf, Aditya M. Limaye, Alexander H. Liu, Michael A. Yusov, Ian W. Hunter, Karthish Manthiram
{"title":"Nonidealities in CO2 Electroreduction Mechanisms Revealed by Automation-Assisted Kinetic Analysis","authors":"Joy S. Zeng, Vineet Padia, Grace Y. Chen, Joseph H. Maalouf, Aditya M. Limaye, Alexander H. Liu, Michael A. Yusov, Ian W. Hunter, Karthish Manthiram","doi":"10.1021/acscentsci.3c01295","DOIUrl":"https://doi.org/10.1021/acscentsci.3c01295","url":null,"abstract":"In electrocatalysis, mechanistic analysis of reaction rate data often relies on the linearization of relatively simple rate equations; this is the basis for typical Tafel and reactant order dependence analyses. However, for more complex reaction phenomena, such as surface coverage effects or mixed control, these common linearization strategies will yield incomplete or uninterpretable results. Cohesive kinetic analysis, which is often used in thermocatalysis and involves quantitative model fitting for data collected over a wide range of reaction conditions, requires more data but also provides a more robust strategy for interrogating reaction mechanisms. In this work, we report a robotic system that improves the experimental workflow for collecting electrochemical rate data by automating sequential testing of up to 10 electrochemical cells, where each cell can have a different electrode, electrolyte, gas-phase reactant composition, and applied voltage. We used this system to investigate the mechanism of carbon dioxide electroreduction to carbon monoxide at several immobilized metal tetrapyrroles. Specifically, at cobalt phthalocyanine (CoPc), cobalt tetraphenylporphyrin (CoTPP), and iron phthalocyanine (FePc), we see signatures of complex reaction mechanisms, where observed bicarbonate and CO<sub>2</sub> order dependences change with applied potential. We illustrate how phenomena such as electrolyte poisoning and potential-dependent degrees of rate control can explain the observed kinetic behaviors. Our mechanistic analysis suggests that CoPc and CoTPP share a similar reaction mechanism, akin to one previously proposed, whereas the mechanism for FePc likely involves a species later in the catalytic cycle as the most abundant reactive intermediate. Our study illustrates that complex reaction mechanisms that are not amenable to common Tafel and order dependence analyses may be quite prevalent across this class of immobilized metal tetrapyrrole electrocatalysts.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141552800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Oxidation States: Intrinsically Ambiguous? 氧化态:本质上模糊不清?
IF 18.2 1区 化学
ACS Central Science Pub Date : 2024-06-25 DOI: 10.1021/acscentsci.4c00825
Isaac F. Leach, Johannes E. M. N. Klein
{"title":"Oxidation States: Intrinsically Ambiguous?","authors":"Isaac F. Leach, Johannes E. M. N. Klein","doi":"10.1021/acscentsci.4c00825","DOIUrl":"https://doi.org/10.1021/acscentsci.4c00825","url":null,"abstract":"The oxidation state (<b><i>OS</i></b>) formalism is a much-appreciated good in chemistry, receiving wide application. However, like all formalisms, limitations are inescapable, some of which have been recently explored. Providing a broader context, we discuss the <b><i>OS</i></b> and its interpretation from a computational perspective for transition metal (TM) complexes. We define a broadly applicable and easy-to-use procedure to derive <b><i>OS</i></b>s based on quantum chemical calculations, via the use of localized orbitals, dubbed the Intrinsic <b><i>OS</i></b>. Applying this approach to a cobalt complex in five <b><i>OS</i></b>s, isolated by Hunter and co-workers ( <cite><i>Inorg. Chem.</i></cite> <span>2021</span>, <em>60</em>, 17445), we find that the calculated Intrinsic <b><i>OS</i></b> matches the formal <b><i>OS</i></b>, consistent with the experimental characterization. Through analysis of the delocalized orbitals, the ligand field of the Co(III) complex is found to be “inverted”, despite every cobalt–ligand bond being classically dative from the localized perspective─a bonding scenario very similar to that of [Cu(CF<sub>3</sub>)<sub>4</sub>]<sup>−</sup>. This is not atypical but rather a natural consequence of these metals bonding in the high-valent region, and we propose a more restrictive definition of (locally) inverted bonding. Additionally, two bonding descriptors within the Intrinsic Bonding Orbital (IBO) framework (σ-gain and π-loss) are introduced, which enable facile quantification of electron-sharing covalency across a broad range of TM complexes.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141549869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Extended Pharmacokinetics Improve Site-Specific Prodrug Activation Using Radiation 扩展药代动力学利用辐射改善特定位点原药活化
IF 18.2 1区 化学
ACS Central Science Pub Date : 2024-06-21 DOI: 10.1021/acscentsci.4c00354
Jeremy M. Quintana, Mikyung Kang, Huiyu Hu, Thomas S. C. Ng, Gregory R. Wojtkiewicz, Ella Scott, Sareh Parangi, Jan Schuemann, Ralph Weissleder, Miles A. Miller
{"title":"Extended Pharmacokinetics Improve Site-Specific Prodrug Activation Using Radiation","authors":"Jeremy M. Quintana, Mikyung Kang, Huiyu Hu, Thomas S. C. Ng, Gregory R. Wojtkiewicz, Ella Scott, Sareh Parangi, Jan Schuemann, Ralph Weissleder, Miles A. Miller","doi":"10.1021/acscentsci.4c00354","DOIUrl":"https://doi.org/10.1021/acscentsci.4c00354","url":null,"abstract":"Radiotherapy is commonly used to treat cancer, and localized energy deposited by radiotherapy has the potential to chemically uncage prodrugs; however, it has been challenging to demonstrate prodrug activation that is both sustained <i>in vivo</i> and truly localized to tumors without affecting off-target tissues. To address this, we developed a series of novel phenyl-azide-caged, radiation-activated chemotherapy drug-conjugates alongside a computational framework for understanding corresponding pharmacokinetic and pharmacodynamic (PK/PD) behaviors. We especially focused on an albumin-bound prodrug of monomethyl auristatin E (MMAE) and found it blocked tumor growth in mice, delivered a 130-fold greater amount of activated drug to irradiated tumor versus unirradiated tissue, was 7.5-fold more efficient than a non albumin-bound prodrug, and showed no appreciable toxicity compared to free or cathepsin-activatable drugs. These data guided computational modeling of drug action, which indicated that extended pharmacokinetics can improve localized and cumulative drug activation, especially for payloads with low vascular permeability and diffusivity and particularly in patients receiving daily treatments of conventional radiotherapy for weeks. This work thus offers a quantitative PK/PD framework and proof-of-principle experimental demonstration of how extending prodrug circulation can improve its localized activity <i>in vivo</i>.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141549870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信