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The Significant and Profound Impacts of Chou’s Distorted Key Theory for Developing peptide drugs

Natural Science 2020年第9期12卷 638-639页

作者： Kuo-Chen Chou Gordon Life Science Institute Boston MA USA

In this short review paper, the significant and profound impacts of the distorted key theory for developing peptide drugs have been briefly recalled with crystal clear convincingness.

关键词： AIDS peptide drugs Distorted Key Theory Microenvironment

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

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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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Current development of bicyclic peptides

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Chinese Chemical Letters 2023年第6期34卷 130-143页

作者： Dazhi Feng Lihua Liu Yuqi Shi Pian Du Shengtao Xu Zheying Zhu Jinyi Xu Hong Yao State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry China Pharmaceutical UniversityNanjing 210009China School of Pharmacy The University of NottinghamUniversity Park CampusNottingham NG72RDUnited Kingdom

Bicyclic peptides,a class of polypeptides with two loops within their structure,have emerged as powerful tools in the development of new peptide *** have the potential to bind to challenged drug targets,with antibody-like affinity and ***,bicyclic peptides possess small molecule-like access to chemical synthesis,which is conducive to large-scale synthesis and *** the last five years,bicyclic peptide technology has been increasingly developed,and researchers have carried out a variety of studies to elucidate the potential functions of bicyclic *** the continuous development of synthetic methods and the advances of new technology to build bicyclic peptide libraries,bicyclic peptides are now becoming widely used in the development of new drugs for various *** perspective provides an overview of the structure types,synthesis and applications of bicyclic peptides in current drug development,and our own views on future challenges of bicyclic peptides.

关键词： peptide therapeutics Bicyclic peptides Protein-protein interaction peptides synthesis peptide drugs

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Advances in oral peptide drug nanoparticles for diabetes mellitus treatment

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Bioactive Materials 2022年第9期7卷 392-408页

作者： Yan Li Wen Zhang Ruichen Zhao Xin Zhang School of Chemistry and Biological Engineering University of Science and Technology BeijingBeijing100083PR China State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing100190PR China School of Chemical Engineering University of Chinese Academy of SciencesBeijing100049PR China

peptide drugs play an important role in diabetes mellitus *** administration of peptide drugs is a promising strategy for diabetes mellitus because of its convenience and high patient compliance compared to parenteral administration ***,there are a series of formidable unfavorable conditions present in the gastrointestinal(GI)tract after oral administration,which result in the low oral bioavailability of these peptide *** overcome these challenges,various nanoparticles(NPs)have been developed to improve the oral absorption of peptide drugs due to their unique in vivo properties and high design *** review discusses the unfavorable conditions present in the GI tract and provides the corresponding strategies to overcome these *** review provides a comprehensive overview on the NPs that have been constructed for oral peptide drug delivery in diabetes mellitus ***,we will discuss the rational application and give some suggestions that can be utilized for the development of oral peptide drug *** aim is to provide a systemic and comprehensive review of oral peptide drug NPs that can overcome the challenges in GI tract for efficient treatment of diabetes mellitus.

关键词： Oral nanoparticles peptide drugs Gastrointestinal tract Diabetes mellitus Oral bioavailability

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Introducing New peptide Extracts from Saccharomyces cerevisiae and Achatina achatina Fluids with Strong Inhibitory Activities on Human α-Amylase

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Journal of Biosciences and Medicines 2022年第11期10卷 226-239页

作者： Ehuie Micaël Bédikou Fafadzi Charlotte Ehon Chadon Christelle Assémian Djary Michel Koffi Bomo Mondesire Kadjo Allah Antoine Assamoi Sebastien Niamké Department of Food Biotechnology Laboratory of Biotechnology Agriculture and Biological Resources Valorization Training and Research Unit in Biosciences University Félix Houphou&euml t-Boigny Abidjan C&ocirc te d’Ivoire

This study aimed at exploring for new natural peptides with strong inhibitory capabilities on α-amylase, the main metabolic enzyme that regulates mellitus diabetes, in order to contribute in controlling this global pandemic. It has consisted in heat shock (to 60°C, 70°C, 80°C, 90°C and 100°C for 10, 20 and 30 minutes) of crude proteins extracted from biomass and extracellular parts of Saccharomyces cerevisiae under cultivation, and from the digestive fluid of the giant snail Achatina achatina, and in-vitro assays of the resulting solutions, as effectors, in human α-amylase catalyzing reactions. The results showed that whatever the temperature and time of treatment, an increase (from 2.65 to 3.98-fold) in proteins concentration was noticed. When blended up to 75 microliters in reaction mixtures, the three peptide extracts showed beyond 11% of inhibition of initial α-amylase activity. By reducing samples volume, only 5 microliters of the studied peptide extracts representing 4.70 μg of S. cerevisiae biomass peptides, 0.55 μg of S. cerevisiae extracellular peptides or 1.05 μg of peptides from the digestive fluid A. achatina were quite sufficient to induce complete (100%) inhibition of the human α-amylase activity. Compared to the inhibitory effect obtained from 2.50 μg of acarbose, a renowned antidiabetic, the studied peptide effectors showed more pronounced inhibitory activities. So, we can positively state that S. cerevisiae as well as A. achatina are both capable of synthesizing proteins made up of small inhibitory peptides which deserve purification and structural analysis for potential exploitation as healthy antidiabetic drugs.

关键词： α-Amylase Inhibitors Healthy Antidiabetics peptide drugs Saccharomyces cerevisiae Achatina achatina

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Design of histidine-rich peptides with enhanced bioavailability and inhibitory activity against hepatitis C virus

Design of histidine-rich peptides with enhanced bioavailabil...

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第十一届中国生物毒素研究及医药应用年会

作者： Wei Hong Runhong Zhang Zhiyong Di Yawen He Zhenhuan Zhao Jun Hu Yingliang Wu Wenxin Li Zhijian Cao State Key Laboratory of Virology College of Life SciencesWuhan University

＜正＞Recently,peptide drugs have evolved into mainstream therapeutics,representing a significant portion of the pharmaceutical ***,their bioavailability remains to be improved compared with that of chemical ***,we screened and identified a new peptide,Ctry2459,from a scorpion venom peptide library that was proven to inhibit hepatitis C virus（HCV） infection via inactivating infectious viral ***,Ctry2459 cannot suppress established infection of HCV because of the poor cellular uptake and restriction of *** on the molecular template of the Ctry2459 peptide,we designed two histidine-rich peptides（Ctry2459-H2 and Ctry2459-H3） with significantly enhanced cellular uptake and improved intracellular ***,the two mutated peptides,as well as the wild-type peptide Ctry2459,exhibited virucidal activities against *** distinct contrast to the Ctry2459 peptide,the mutated peptides significantly suppressed the established HCV infection at the cellular level but demonstrated lower cytotoxic and hemolytic *** work presents an effective design strategy for optimizing natural antiviral peptides and opens a new avenue for enhancing the bioavailability of peptide drugs.

关键词： peptide drugs Histidine-rich peptides Cellular uptake Endosomal escape Bioavailability Anti-HCV

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Modulating peptides' biophysical properties and biological functions

Modulating peptides' biophysical properties and biological f...

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第十一届全国化学生物学学术会议

作者：李子刚北京大学深圳研究生院

Continuous efforts have been invested in developing constrained peptides for modulating PPIs by enhancing the peptides’ helicity.A precisely-positioned in-tether chiral center was found to be able to modulate a peptide’s helicity and cell permeability. This chirality induced helicity(CIH) concept was then translated into a N-terminus aspartic acid linkage(TD) for more facile peptide synthesis. The stabilized peptides constructed with these methods were utilized to target different intracellular protein targets including MDM2,ERα and HDAC family proteins both in vitro and in vivo. Notably,PROTAC strategy could also be applied with stabilized peptides.

关键词： Protein stable peptide protein and protein interaction peptide drugs epigenetics

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