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Recent advances in chemical protein synthesis:method developments and biological applications

Science China Chemistry 2024年第4期67卷 1060-1096页

作者： Suwei Dong Ji-Shen Zheng Yiming Li Huan Wang Gong Chen Yongxiang Chen Gemin Fang Jun Guo chunmao he Honggang Hu Xuechen Li Yanmei Li Zigang Li Man Pan Shan Tang Changlin Tian Ping Wang Bian Wu Chuanliu Wu Junfeng Zhao Lei Liu State Key Laboratory of Natural and Biomimetic Drugs and School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Division of Life Sciences and Medicine University of Science and Technology of ChinaHefei 230027China School of Food and Biological Engineering Engineering Research Center of Bio-processMinistry of EducationHefei University of TechnologyHefei 230009China School of Chemistry and Chemical Engineering Nanjing UniversityNanjing 210023China State Key Laboratory of Elemento-Organic Chemistry Nankai UniversityTianjin 300071China Department of Chemistry Tsinghua UniversityBeijing 100084China Institute of health Sciences Anhui UniversityHefei 230601China College of Chemistry Central China Normal UniversityWuhan 430079China School of Chemistry and Chemical Engineering South China University of TechnologyGuangzhou 510640China School of Medicine or Institute of Translational Medicine Shanghai UniversityShanghai 200444China Department of Chemistry The University of Hong KongHong Kong 999077China Shenzhen Graduate School Peking UniversityShenzhen 518055China School of Chemistry and Chemical Engineering Shanghai Jiao Tong UniversityShanghai 200240China School of Life Sciences University of Science and Technology of ChinaHefei 230026China Department of Chemical Biology Shanghai Jiao Tong UniversityShanghai 200240China Institute of Microbiology Chinese Academy of SciencesBeijing 100101China Department of Chemistry Xiamen UniversityXiamen 361005China School of Pharmaceutical Science Guangzhou Medical UniversityGuangzhou 511436China

The central dogma of modern biology underscores the pivotal roles proteins play in diverse biological processes,the study of which necessitates advanced methods to produce proteins with precision and *** protein synthesis,a powerful approach utilizing chemical reactions for the de novo construction of structurally accurate proteins,has emerged as a transformative tool for studying proteins and generating protein derivatives/mimics inaccessible by natural biological machinery,including post-translationally modified proteins,proteins comprised of unnatural amino acids,as well as mirror-image *** review summarizes recent strides in synthetic method developments for chemical protein synthesis,including innovative techniques in solid-phase peptide synthesis,the challenges presented by difficult sequences in either synthesis or folding and the exploration of novel ligation reactions using both chemical and enzymatic ***,the review also delves into newly developed protocols for site-selective protein modifications and the generation of stapled or macrocyclized peptides/miniproteins,highlighting the power of chemical methods to make structurally diverse *** applications of synthetic proteins in investigating post-translational modifications(phosphorylation,lipidation,glycosylation,ubiquitination,etc.),mirror-image biological processes and drug development are further ***,these topics provide a comprehensive overview of the current landscape of chemical protein synthesis.

关键词： chemical protein synthesis solid-phase peptide synthesis ligation reactions post-translational modifications mirror-image proteins peptide drugs

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Chemical protein synthesis elucidates key modulation mechanism of the tyrosine-O-sulfation in inducing strengthened inhibitory activity of hirudin

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Chinese Chemical Letters 2023年第5期34卷 213-216页

作者： Ye Yang Mingchan Liang Rui Wang chunmao he School of Chemistry and Chemical Engineering South China University of TechnologyGuangzhou 510640China Pingshan translational medicine center Shenzhen Bay LaboratoryShenzhen 518118China

Tyrosine sulfation is an important post-translational modification that enhances the inhibitory activity of ***,we developed a facile synthetic strategy to afford the sulfated hirudins with up to three modifications and in multi-milligram scales,after a single HPLC purification *** these synthetic proteins,a novel type of modulation mechanism exhibited by tyrosine sulfation was proposed,which would help to delineate the structure-function relationships in other sulfated proteins and more importantly,to serve as a basis for the development of related antithrombotic agents.

关键词： Tyrosine sulfation Hirudin Chemical protein synthesis Post-translational modification Native chemical ligation

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Insertion of unnatural metal ligand in the heme pocket of nitrophorin through protein semi-synthesis:Toward biomimicking binuclear active sites

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Chinese Chemical Letters 2023年第12期34卷 132-135页

作者： Yonglu Chen Yi Zhou chunmao he School of Chemistry and Chemical Engineering South China University of TechnologyGuangzhou 510640China

herein,we report a semi-synthetic strategy affording a nitrophorin 2(NP2)variant with a N,N'-bis(2-pyridylmethyl)amine(Dpa)ligand as sidechain selectively installed at position 27,which was assembled from a synthetic peptide thioester bearing the Dpa ligand and an expressed protein segment via native chemical *** semi-synthetic NP2 was able to accept the natural heme b cofactor and the Dpa ligand was able to bind Cu(Ⅱ)/Fe(Ⅲ)ions,leading to heteronuclear active site.

关键词： Protein semi-synthesis Protein modification Nitrophorin2 heteronuclear active site Native chemical ligation

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A mini-review on the enzyme-mediated manipulation of proteins/peptides

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Chinese Chemical Letters 2018年第7期29卷 1017-1021页

作者： Shaomin Lin chunmao he School of Chemistry and Chemical Engineering South China University of Technology

Recent years have seen an ever increasing number of enzyme mediated protein/peptide modification reactions, which contribute significantly to the elucidation of related biological functions. The many available enzymes have, however, caused difficulties for practitioners in choosing the most appropriate enzyme for a certain purpose. This review surveyed the widely used enzymes(i.e., sortases, butelase 1,subtiligase, formylglycine generating enzyme and farnesyltransferase) in the manipulation of proteins/peptides, and the application fields of these enzymes as well as the advantages and limitations of each enzyme are summarized.

关键词： Protein modification Protein labeling Protein ligation Site-selective Enzyme-mediated

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Single-cell analyses identify anaphase-promoting complex subunit 11 as a switch controlling neuronal differentiation of glioblastoma cells

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Genes & Diseases 2023年第5期10卷 1802-1805页

作者： Runwei Yang Ziyu Wang Songtao Qi Bowen Ni Jinglin Guo Kaishu Li Haimin Song Sidi Xie Yunxiao Zhang Xirang Wang chunmao he Guanglong Huang Yawei Liu Department of Neurosurgery Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Department of Neurosurgery Shunde HospitalSouthern Medical UniversityFoshanGuangdong 528300China Medical Research Center Shunde HospitalSouthern Medical UniversityFoshanGuangdong 528300China Department of Neurosurgery The Sixth Affiliated Hospital of Guangzhou Medical UniversityQingyuan People's HospitalQingyuanGuangdong 511518China School of Chemistry and Chemical Engineering South China University of TechnologyGuangzhouGuangdong 510640China

Glioblastoma(GBM)is the most common and lethal malignancy in the central nervous system.1 One of the major difficulties in treatment is that the initial clinical diagnosis of GBM is already WHO grade IV,without recognizable lower-grade precursor *** number variations(CNVs)were found to appear in malignant cells several years before the initial diagnosis of GBM.2 Less differentiation and more aggressive phenotypes were observed in GBM cells with a higher degree of CNVs.3 Additionally,CNVs provide more accurate stratification of clinical outcomes than does the WHO grade system.4 Therefore,we reasoned that differentially expressed genes(DEGs)among GBM cells with different CNV statuses would be significant for the aggressiveness of *** we leveraged the single-cell RNA-sequencing(scRNA-seq)to construct the CNV profile of GBM at single-cell resolution,divided GBM cells into different clusters according to their CNV statuses,and investigated the molecular functions of DEGs among GBM *** a series of experiments,we identified anaphase-promoting complex subunit 11(ANAPC11)as a switch controlling the neuronal differentiation of GBM cells,providing a novel alternative for the development of differentiation-inducing therapy to overcome GBM.

关键词： diagnosis controlling system.

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Three rare anti-inflammatory sesquiterpene lactones from Magnolia grandiflora

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Chinese Journal of Natural Medicines 2024年第3期22卷 265-272页

作者： XU Shuangyu ZHANG Feng TAO Linlan JIANG Yangming HUANG Tao LI Yanan HU Zhanxing YANG Jue HAO Xiaojiang YUAN chunmao State Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical UniversityGuiyang 550014China School of Pharmaceutical Sciences Guizhou Medical UniversityGuiyang 550025China Natural Products Research Center of Guizhou Province Guiyang 550014China State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of BotanyChinese Academy of SciencesKunming 650201China

Four new sesquiterpene lactones(SLs)(1–4),along with a biosynthetically related SL(5),have been isolated from the leaves of Magnolia *** A(1)is notable as the first C18 homogemarane type SL,featuring a unique 1,7-dioxaspiro[4.4]nonan-6-one *** 2 and 3,representing the first instances of chlorine-substituted gemarane-type SL analogs in natural products,were also *** structures of these isolates were elucidated through a combination of spectroscopic data analysis,electronic circular dichroism calculations,and X-ray single-crystal diffraction *** isolates demonstrated anti-inflammatory activity in lipopolysaccharide-stimulated RAW264.7 ***,3–5 showed a significant inhibitory effect on nitric oxide production,with IC50 values ranging from 0.79 to 4.73μmol·L^(−1).Additionally,4 and 5 exhibited moderate cytotoxic activities against three cancer cell lines,with IC50 values between 3.09 and 11.23μmol·L^(−1).

关键词： Magnolia grandiflora Sesquiterpene lactones Isolation and identification Anti-inflammatory activity

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基于STM32的EtherCAT与UDP实时通信转换的设计与实现

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现代工业经济和信息化 2023年第4期13卷 111-113页

作者：何春茂葛智光广东省高性能伺服系统企业重点实验室广东珠海519000 珠海格力电器股份有限公司广东珠海519000

由于EtherCAT现场总线的开源性,在国内工业自动化领域应用越来越广。EtherCAT现场总线具有很强的实时性要求,通信抖动小,周期短。工控机端的通信网络一般为TCP/IP通信协议,该协议为非实时性通信方式,不能与EtherCAT直接完成数据交互,两... 详细信息

由于EtherCAT现场总线的开源性,在国内工业自动化领域应用越来越广。EtherCAT现场总线具有很强的实时性要求,通信抖动小,周期短。工控机端的通信网络一般为TCP/IP通信协议,该协议为非实时性通信方式,不能与EtherCAT直接完成数据交互,两者之间需要进行通信协议的转换。设计了一种基于STM32的EtherCAT从站和FPGA的UDP的通信方式,通过借助硬件介质来实现,硬件开发采用LAN9252 (EtherCAT从站控制器)、STM32F103、FPGA和88EE1111为主要芯片。在STM32F103中执行EtherCat从站协议栈,FPGA实现UDP与EtherCAT协议的转换,实现实时通信的转换及传输。

关键词： STM32F103 EtherCAT FPGA UDP 通信转换

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基坑开挖对下卧盾构隧道的影响风险分析

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沈阳建筑大学学报（自然科学版） 2015年第1期31卷 62-70页

作者：何连昇何春茂张俊东北大学审计处辽宁沈阳110819 东北大学基建管理处辽宁沈阳110819 东北大学资源与土木工程学院辽宁沈阳110819

目的研究基坑开挖对邻近既有下卧盾构隧道结构产生的附加应力及不均匀变形,为施工阶段既有隧道的风险评估及控制措施提供参考.方法以哈大客专沈阳站房改造工程为背景,探讨了基坑开挖卸载对下卧盾构隧道造成的主要风险因素及盾构管片破... 详细信息

目的研究基坑开挖对邻近既有下卧盾构隧道结构产生的附加应力及不均匀变形,为施工阶段既有隧道的风险评估及控制措施提供参考.方法以哈大客专沈阳站房改造工程为背景,探讨了基坑开挖卸载对下卧盾构隧道造成的主要风险因素及盾构管片破坏的类型,针对土体力学参数的空间变异性及随机性引入蒙特卡洛模拟与三维有限元相结合的方法对衬砌结构的风险事故发生概率进行定量分析.结果基坑开挖卸载之后,隧道横向位移及管片最大压应力超出规定值的概率均为0;上抬变形量及管片最大拉应力超出规定值概率分别为39.8%、2.29%.多种因素下盾构管片总失效概率为41.18%.结论基坑开挖方法要遵循减少单次卸荷量及隧道穿越跨度的原则,并且开挖后应尽量减少基坑的放置时间.

关键词：基坑工程施工阶段风险分析蒙特卡洛失效概率

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筏板基础大体积混凝土裂缝的数值模拟及施工质量控制

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沈阳建筑大学学报（自然科学版） 2010年第5期26卷 913-919页

作者：余祖国何春茂东北大学基建管理处辽宁沈阳110004

目的分析高层建筑筏板基础施工中大体积混凝土裂缝出现原因,提出在施工过程中应采取的措施,确保工程质量.方法以一个天然地基筏板基础的工程为实例,采用有限元方法筏形基础沉降计算程序,对施工过程进行数值模拟,分析了裂缝产生的原因,... 详细信息

目的分析高层建筑筏板基础施工中大体积混凝土裂缝出现原因,提出在施工过程中应采取的措施,确保工程质量.方法以一个天然地基筏板基础的工程为实例,采用有限元方法筏形基础沉降计算程序,对施工过程进行数值模拟,分析了裂缝产生的原因,从施工技术角度出发,从选料、配合比设计、施工方法、控制入模温度和测温、养护等方面,提出一系列综合性措施,并使其沉降和差异沉降量都能满足规范规定的要求.结果分析表明温度应力是大体积混凝土出现裂缝的最主要内在原因,人为因素是重要诱因,通过施工过程中的质量控制能有效地保证工程质量.结论为有效地控制大体积混凝土的裂缝产生提供了一个很好的实例,对大体积混凝土的裂缝预防有一定的参考价值.

关键词：筏板基础质量控制温度应力施工要点

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高师院校“幼儿教师职业道德”课程教学改革的路径探索

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四川职业技术学院学报 2024年第2期34卷 58-61页

作者：任春茂何芳遵义师范学院教师教育学院贵州遵义563006

随着社会对幼儿教师职业道德的不断重视,“幼儿教师职业道德”课程已成为高师院校学前专业的必修课,但由于教学内容、教学方式方法等存在问题,使得“幼儿教师职业道德”的课程教学效果不理想,“准幼儿教师”的职业素养较差。因此,应从... 详细信息

随着社会对幼儿教师职业道德的不断重视,“幼儿教师职业道德”课程已成为高师院校学前专业的必修课,但由于教学内容、教学方式方法等存在问题,使得“幼儿教师职业道德”的课程教学效果不理想,“准幼儿教师”的职业素养较差。因此,应从优化课程内容、改革教学方式方法、强化“准幼儿教师”职业生活体验、加强隐性职业道德课程建设等方面对高师院校“幼儿教师职业道德”课程进行教学改革,整体提升“准幼儿教师”的职业道德素养。

关键词：高师院校职业道德课程教学

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