ChemRxiv : the preprint server for chemistry最新文献_第2页

Leveraging molecular structure and bioactivity with chemical language models for drug design 利用分子结构和生物活性的化学语言模型进行药物设计

ChemRxiv : the preprint server for chemistry Pub Date : 2021-10-04 DOI: 10.33774/chemrxiv-2021-xzgst

Michael Moret, F. Grisoni, Cyrill Brunner, G. Schneider

引用次数: 1

Structure-Activity-Relationship and Bioactivity of Neurotrophic trans-Banglene 神经营养反式邦烯的构效关系及生物活性研究

ChemRxiv : the preprint server for chemistry Pub Date : 2021-10-04 DOI: 10.33774/chemrxiv-2021-0b2wc

K. Gohil, M. Kazmi, Florence Williams

{"title":"Structure-Activity-Relationship and Bioactivity of Neurotrophic trans-Banglene","authors":"K. Gohil, M. Kazmi, Florence Williams","doi":"10.33774/chemrxiv-2021-0b2wc","DOIUrl":"https://doi.org/10.33774/chemrxiv-2021-0b2wc","url":null,"abstract":"Neurotrophic small molecule natural products are functional analogs of signaling proteins called neurotrophins, which cause a pro-growth, pro-survival, or pro-differentiation response in neuronal cells. While these phenotypic responses are desirable to combat neurodegenerative disease progression, neurotrophin proteins possess pharmacokinetic properties that present challenges to their administration in living organisms, whether in biomedical studies or as therapeutics. Small molecules such as the cis- and trans-banglenes offer attractive alternatives to activate neurotrophic responses. We describe the synthesis and testing of banglene derivatives to establish a structure-activity response for the banglene family. Notably, during the course of our studies trans-banglene was shown to cause nerve growth factor (NGF)-potentiated neuritogenesis that was markedly stronger than the neuritogenic effects of trans-banglene alone. We demonstrate that only (–) trans-banglene is active, while its (+) enantiomer is not, and further demonstrate that select modifications on the cyclohexene ring of trans-banglene does not impair its bioactivity. Finally, to probe the relationship between (–) trans-banglene’s mechanism of ac-tion and canonical NGF signal transduction pathways, we employed kinase inhibitors targeting Pkc, Akt1/2/3 and Erk1/2, designed to inhibit NGF-induced neurotrophic signaling. Interestingly, (–) trans-banglene potentiation of NGF-induced neuri-togenesis was unaffected by the presence of these kinase inhibitors. Collectively, these results suggest a dual-mode of action for (–) trans-banglene (both neurotrophic alone and strongly potentiating of NGF activity), and an independence of its po-tentiating action on Pkc and Erk1/2 enzymatic activity.","PeriodicalId":72565,"journal":{"name":"ChemRxiv : the preprint server for chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42238041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Donor-Acceptor Pyridinium Salts for Photo-Induced Electron Transfer Driven Modification of Tryptophan in Peptides, Proteins, and Proteomes using Visible Light 利用可见光对多肽、蛋白质和蛋白质组中的色氨酸进行光诱导电子转移修饰的供体-受体吡啶盐

ChemRxiv : the preprint server for chemistry Pub Date : 2021-10-04 DOI: 10.33774/chemrxiv-2021-r2nd2

C. Hoopes, Francisco García, A. Sarkar, Nicholas J Kuehl, D. Barkan, N. Collins, Chien-Hsang Hsu, Michael K. Jones, M. Schirle, Michael T. Taylor

{"title":"Donor-Acceptor Pyridinium Salts for Photo-Induced Electron Transfer Driven Modification of Tryptophan in Peptides, Proteins, and Proteomes using Visible Light","authors":"C. Hoopes, Francisco García, A. Sarkar, Nicholas J Kuehl, D. Barkan, N. Collins, Chien-Hsang Hsu, Michael K. Jones, M. Schirle, Michael T. Taylor","doi":"10.33774/chemrxiv-2021-r2nd2","DOIUrl":"https://doi.org/10.33774/chemrxiv-2021-r2nd2","url":null,"abstract":"Tryptophan (Trp) plays a variety of critical functional roles in protein biochemistry however, owing to its low natural frequency and poor nucleophilicity, the design of effective methods for both single protein bioconjugation at Trp as well as for in situ chemoproteomic profiling re-mains a challenge. Here, we report a method for covalent Trp modification that is suitable for both scenarios by invoking photo-induced electron transfer (PET) as a means of driving efficient reactivity. We have engineered biaryl N-carbamoyl pyridinium salts that possess a donor-acceptor relationship enabling optical triggering with visible light whilst simultaneously attenuating the probe’s photo-oxidation potential in order to prevent photodegradation. This probe was assayed against a small bank of eight peptides and proteins, where it was found that micromolar concentrations of probe and short irradiation times (10-60 min) with violet light enabled efficient reactivity towards surface exposed Trp residues. The carbamate transferring group can be used to transfer useful functional groups to proteins including affinity tags and click handles. DFT calculations and other mechanistic analyses reveal correlations between excited state lifetimes, relative fluorescent quantum yields, and chemical reactivity. Biotinylated and azide-functionalized pyridinium salts were used for Trp profiling in HEK293T lysates and in situ in HEK293T cells using 450 nm LED irradiation. Peptide level enrichment from live cell labelling experiments identified 290 Trp modifications, with an 82% selectivity for Trp modification over other π-amino acids; demonstrating the ability of this method to identify and quantify reactive Trp residues from live cells.","PeriodicalId":72565,"journal":{"name":"ChemRxiv : the preprint server for chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43245797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Effect of the degree of protonation of amino acid dopants in Chirality amplification in DSCG Lyotropic Nematic phases. 氨基酸掺杂物质子化程度对DSCG溶向相手性扩增的影响。

ChemRxiv : the preprint server for chemistry Pub Date : 2021-10-04 DOI: 10.33774/chemrxiv-2021-5r8gf

F. Berride, Eduardo Troche-Pesqueira, R. Weiss, A. Navarro‐Vázquez, M. Cid

引用次数: 1

Computer Quiz Games in General Chemistry for Engineering Majors in an English as a Second Language Environment 英语作为第二语言环境下工程专业普通化学计算机测验游戏

ChemRxiv : the preprint server for chemistry Pub Date : 2021-10-01 DOI: 10.33774/chemrxiv-2021-5g682

S. S. Ling, Fabrice Saffre, Deborah L. Gater, L. Halim, A. Isakovic

引用次数: 0

Absolute Configuration of Bromofluoroiodomethane after Preparative Gas Chromatographic Separation 制备气相色谱分离后溴代碘甲烷的绝对构型

ChemRxiv : the preprint server for chemistry Pub Date : 2021-10-01 DOI: 10.33774/chemrxiv-2021-51rbh

B. Spenger, Stefan Näf, S. Manov, J. Stohner

引用次数: 0

Upper Secondary School and University Level Students’ Perceptions of Extractions in Context: Experiences from a Simple Laboratory Experiment 从一个简单的实验室实验看高中和大学学生对上下文提取的感知

ChemRxiv : the preprint server for chemistry Pub Date : 2021-10-01 DOI: 10.33774/chemrxiv-2021-wdrwc

Tuomas M. A. Nurmi, J. Siitonen

{"title":"Upper Secondary School and University Level Students’ Perceptions of Extractions in Context: Experiences from a Simple Laboratory Experiment","authors":"Tuomas M. A. Nurmi, J. Siitonen","doi":"10.33774/chemrxiv-2021-wdrwc","DOIUrl":"https://doi.org/10.33774/chemrxiv-2021-wdrwc","url":null,"abstract":"We discuss the pedagogical challenges associated with the current way of introducing extraction in upper secondary school chemistry education. These challenges were identified based on a survey of upper secondary school textbooks and verified through a questionnaire study. To address the identified challenges, we introduce a simple and effective extraction experiment which focuses on building a deeper conceptual understanding of extraction processes. The operationally simple extraction experiment and the accompanying questionnaire revealed that while students have several chemical misconceptions arising from the use of superficial everyday examples, they have all the necessary knowledge for developing a deeper understanding of chemistry. Providing a suitable experimental platform for developing and re-evaluating their knowledge allows the students to reasonably independently re-conceptualize their thinking toward a more coherent view of the surrounding world and the related scientific models. Furthermore, the work analyses the challenges that can be encountered when using everyday examples in teaching, and demonstrates that student-discovered examples of chemical systems can be a powerful method for generating meaningful and relevant ways to introduce scientific phenomena in STEM education.","PeriodicalId":72565,"journal":{"name":"ChemRxiv : the preprint server for chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49564826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Online tools to easily build augmented reality models of biomolecules that run right on the web 在线工具，可轻松构建在网络上运行的生物分子增强现实模型

ChemRxiv : the preprint server for chemistry Pub Date : 2021-10-01 DOI: 10.33774/chemrxiv-2021-bj119

Fabio Cortés Rodríguez, M. dal Peraro, L. Abriata

{"title":"Online tools to easily build augmented reality models of biomolecules that run right on the web","authors":"Fabio Cortés Rodríguez, M. dal Peraro, L. Abriata","doi":"10.33774/chemrxiv-2021-bj119","DOIUrl":"https://doi.org/10.33774/chemrxiv-2021-bj119","url":null,"abstract":"Several groups developed in the last years augmented and virtual reality (AR/VR) programs and apps to visualize 3D molecules, most rather static, limited in content, and requiring software installs, some even requiring specialized hardware. During the Covid-19 pandemic, our team launched moleculARweb (https://molecularweb.epfl.ch), a website that offers interactive content for chemistry and structural biology education through web-based AR that works on consumer devices like smartphones, tablets and laptops. The website quickly got thousands of student and teacher users, a substantial fraction of them accessing from their homes given the pandemic. Teachers have been increasingly requesting more biological macromolecules to be available in AR, a demand that we cannot satisfy individually. Therefore, to allow them to build their own material, and also to help us expedite development of activities, we built a web interface where any user can build any online AR experience in few steps starting from a PDB structure or from virtual objects/scenes exported from VMD. We here briefly describe the tool, that is accessible at https://molecularweb.epfl.ch/pages/pdb2ar.html.","PeriodicalId":72565,"journal":{"name":"ChemRxiv : the preprint server for chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45986231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identifying sources of D-serine in Caenorhabditis elegans and their impact on behavior 秀丽隐杆线虫D-丝氨酸来源的鉴定及其对行为的影响

ChemRxiv : the preprint server for chemistry Pub Date : 2021-10-01 DOI: 10.33774/chemrxiv-2021-mz0tt

Tiancheng Qiu, Harvey M. Andersen, Nissa J. Larson, N. Schroeder, J. Sweedler

引用次数: 0

Mechanism and Origin of Remote Stereocontrol in the Organocatalytic C(sp2)-H Alkylation using Nitroalkanes as Alkylating Agents 硝基烷烃烷基化有机催化C（sp2）-H烷基化过程中远程立体控制的机理及来源

ChemRxiv : the preprint server for chemistry Pub Date : 2021-10-01 DOI: 10.33774/chemrxiv-2021-x5mkp

S. C. Mallojjala, Rahul Sakar, Rachael W. Karugu, M. Manna, S. Mukherjee, Jennifer S. Hirschi

引用次数: 1