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The Significant and Profound Impacts of Chou’s Distorted Key Theory for Developing Peptide Drugs 被引量:1
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作者 Kuo-Chen Chou 《Natural Science》 2020年第9期638-639,共2页
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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Advances in oral peptide drug nanoparticles for diabetes mellitus treatment 被引量:6
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作者 Yan Li Wen Zhang +1 位作者 Ruichen Zhao Xin Zhang 《Bioactive Materials》 SCIE 2022年第9期392-408,共17页
Peptide drugs play an important role in diabetes mellitus treatment.Oral administration of peptide drugs is a promising strategy for diabetes mellitus because of its convenience and high patient compliance compared to... Peptide drugs play an important role in diabetes mellitus treatment.Oral administration of peptide drugs is a promising strategy for diabetes mellitus because of its convenience and high patient compliance compared to parenteral administration routes.However,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 drugs.To 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 flexibility.This review discusses the unfavorable conditions present in the GI tract and provides the corresponding strategies to overcome these challenges.The review provides a comprehensive overview on the NPs that have been constructed for oral peptide drug delivery in diabetes mellitus treatment.Finally,we will discuss the rational application and give some suggestions that can be utilized for the development of oral peptide drug NPs.Our 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. 展开更多
关键词 Oral nanoparticles peptide drugs Gastrointestinal tract Diabetes mellitus Oral bioavailability
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Exploration of Target Spaces in the Human Genome for Protein and Peptide Drugs
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作者 Zhongyang Liu Honglei Li +8 位作者 Zhaoyu Jin Yang Li Feifei Guo Yangzhige He Xinyue Liu Yaning Qi Liying Yuan Fuchu He Dong Li 《Genomics, Proteomics & Bioinformatics》 SCIE CAS CSCD 2022年第4期780-794,共15页
After decades of development,protein and peptide drugs have now grown into a major drug class in the marketplace.Target identification and validation are crucial for the discovery of protein and peptide drugs,and bioi... After decades of development,protein and peptide drugs have now grown into a major drug class in the marketplace.Target identification and validation are crucial for the discovery of protein and peptide drugs,and bioinformatics prediction of targets based on the characteristics of known target proteins will help improve the efficiency and success rate of target selection.However,owing to the developmental history in the pharmaceutical industry,previous systematic exploration of the target spaces has mainly focused on traditional small-molecule drugs,while studies related to protein and peptide drugs are lacking.Here,we systematically explore the target spaces in the human genome specifically for protein and peptide drugs.Compared with other proteins,both successful protein and peptide drug targets have many special characteristics,and are also significantly different from those of small-molecule drugs in many aspects.Based on these features,we develop separate effective genome-wide target prediction models for protein and peptide drugs.Finally,a user-friendly web server,Predictor Of Protein and Pept Ide drugs’therapeutic Targets(POPPIT)(http://poppit.ncpsb.org.cn/),is established,which provides not only target prediction specifically for protein and peptide drugs but also abundant annotations for predicted targets. 展开更多
关键词 Protein drug peptide drug Target analysis Target prediction Web server
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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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作者 Ehuie Micaël Bédikou Fafadzi Charlotte Ehon +4 位作者 Chadon Christelle Assémian Djary Michel Koffi Bomo Mondesire Kadjo Allah Antoine Assamoi Sebastien Niamké 《Journal of Biosciences and Medicines》 CAS 2022年第11期226-239,共14页
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 p... 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&deg;C, 70&deg;C, 80&deg;C, 90&deg;C and 100&deg;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. 展开更多
关键词 α-Amylase Inhibitors Healthy Antidiabetics peptide drugs Saccharomyces cerevisiae Achatina achatina
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Current development of bicyclic peptides
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作者 Dazhi Feng Lihua Liu +5 位作者 Yuqi Shi Pian Du Shengtao Xu Zheying Zhu Jinyi Xu Hong Yao 《Chinese Chemical Letters》 SCIE CAS CSCD 2023年第6期130-143,共14页
Bicyclic peptides,a class of polypeptides with two loops within their structure,have emerged as powerful tools in the development of new peptide drugs.They have the potential to bind to challenged drug targets,with an... Bicyclic peptides,a class of polypeptides with two loops within their structure,have emerged as powerful tools in the development of new peptide drugs.They have the potential to bind to challenged drug targets,with antibody-like affinity and selectivity.Meanwhile,bicyclic peptides possess small molecule-like access to chemical synthesis,which is conducive to large-scale synthesis and screening.In 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 peptides.With 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 diseases.This 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. 展开更多
关键词 peptide therapeutics Bicyclic peptides Protein-protein interaction peptides synthesis peptide drugs
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Recent advances in chemical protein synthesis:method developments and biological applications
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作者 Suwei Dong Ji-Shen Zheng +18 位作者 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 《Science China Chemistry》 SCIE EI CAS CSCD 2024年第4期1060-1096,共37页
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 versatility.Chemi... 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 versatility.Chemical 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 proteins.This 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 methods.Furthermore,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 proteins.Recent applications of synthetic proteins in investigating post-translational modifications(phosphorylation,lipidation,glycosylation,ubiquitination,etc.),mirror-image biological processes and drug development are further discussed.Together,these topics provide a comprehensive overview of the current landscape of chemical protein synthesis. 展开更多
关键词 chemical protein synthesis solid-phase peptide synthesis ligation reactions post-translational modifications mirror-image proteins peptide drugs
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Peptide stapling with the retention of double native side-chains
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作者 Ye Wu Yan Zou +4 位作者 Lingling Sun Alfredo Garzino-Demo Honggang Hu Weidong Zhang Xiang Li 《Chinese Chemical Letters》 SCIE CAS CSCD 2021年第12期4045-4048,共4页
All-hydrocarbon stapling strategy has been widely applied for enhancing the proteolytic stability of peptides. However, two major technical hurdles to some extent limit the development of stapled peptides for therapeu... All-hydrocarbon stapling strategy has been widely applied for enhancing the proteolytic stability of peptides. However, two major technical hurdles to some extent limit the development of stapled peptides for therapeutic usage: rational selection of the stapling sites and the corresponding deletion of the native side chains. Previously we described the development of the olefin-terminated amino acids with the retention of native side chains and successfully applied them in the synthesis of hydrocarbon stapled peptides with single side-chain retention. Here, we explored the feasibility and effectiveness of hydrocarbon stapling strategy characterized as double side-chains retention. Modeled after a lengthy human immunodeficiency virus-1(HIV-1) fusion inhibitor SC34 EK, Leu^(i), Ser^(i+4)and Lys^(i), Leu^(i+4)stapled peptides with the retention of double side-chains were effectively obtained. Our complementary study provided a convenient alternative to address where to install the staple in sequence for conventional all-hydrocarbon peptide stapling. Furthermore, this method not only conferred conformational reinforcement for SC34 EK with high α-helicity and protease resistance, but also preserved the structural characteristic(key peripheral residues, charge and solubility) of the linear peptide to the maximum, which are crucial for anti-HIV-1 activity. 展开更多
关键词 Stapling strategy Stapled peptide Native side chain peptide drug design HIV-1 fusion inhibitor SC34EK
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Significance and strategies in developing delivery systems for bio-macromolecular drugs 被引量:2
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作者 Huining HE Qiuling LIANG +6 位作者 Meong Cheoi SHIN Kyuri LEE Junbo GONG Junxiao YE Quan LIU Jingkang WANG Victor YANG 《Frontiers of Chemical Science and Engineering》 SCIE EI CAS CSCD 2013年第4期496-507,共12页
Successful development of a new drug is prohibitively expensive, and is estimated to cost approxi- mately S100-500 million US dollars for a single clinical drug. Yet, a newly developed drug can only enjoy its patent p... Successful development of a new drug is prohibitively expensive, and is estimated to cost approxi- mately S100-500 million US dollars for a single clinical drug. Yet, a newly developed drug can only enjoy its patent protection for 18 years, meaning that after this protected time period, any company can manufacture this product and thus the profit generated by this drug entity would reduce dramatically. Most critically, once a drug is being synthesized, its physical, chemical, and biological attri- butes such as bioavailability and in vivo pharmacokinetics are all completely fixed and cannot be changed. In principal and practice, only the application of an appro- priately designed drug delivery system (DDS) is able to overcome such limitations, and yet the cost of developing a novel drug delivery system is less than 10% of that of developing a new drug. Because of these reasons, the new trend in pharmaceutical development has already begun to shift from the single direction of developing new drugs in the past to a combined mode of developing both new drugs and innovative drug delivery systems in this century. Hence, for developing countries with relatively limited financial resources, a smart strategic move would be to focus on the development of new DDS, which has a significantly higher benefit/risk ratio when comparing to the development of a new drug. Because of the unmatched reaction efficiency and a repetitive action mode, the therapeutic activity of a single bio-macromolecular drug (e.g., protein toxins, gene products, etc.) is equivalent to about 10^6- 10^8 of that from a conventional small molecule anti-cancer agent (e.g., doxorubicin). Hence, bio-macromolecular drugs have been recognized around the world as the future "drug-of-choice". Yet, among the 〉 10000 drugs that are currently available, only -150 of them belong to these bio- macromolecular drugs (an exceedingly low 1.2%), reflect- ing the difficulties of utilizing these agents in clinical practice. In general, the bottleneck limitations of these bio- macromolecular drugs are two-fold: (1) the absence of a preferential action of the drug on tumor cells as opposed to normal tissues, and (2) the lack of ability to cross the tumor cell membrane. In this review, we provide strategies of how to solve these problems simultaneously and collec- tively via the development of innovative drug delivery systems. Since worldwide progress on bio-macromolecular therapeutics still remains in the infant stage and thus open for an equal-ground competition, we wish that this review would echo the desire to industrialized countries such as China to set up its strategic plan on developing delivery systems for these bio-macromolecular drugs, thereby realizing their clinical potential. 展开更多
关键词 delivery systems bio-macromolecular drugs cell penetrating peptides
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A perspective on general direction and challenges facing antimicrobial peptides 被引量:4
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作者 Meng Zhu Peng Liu Zhong-Wei Niu 《Chinese Chemical Letters》 SCIE CAS CSCD 2017年第4期703-708,共6页
The emergence of drug resistant bacterium threatens the global public healthcare systems.The urgent need to obtain new antimicrobials has driven antimicrobial peptides(AMPs) research into spotlight.Here we give a br... The emergence of drug resistant bacterium threatens the global public healthcare systems.The urgent need to obtain new antimicrobials has driven antimicrobial peptides(AMPs) research into spotlight.Here we give a brief introduction of the recent progress of AMPs regarding their structures,properties,production and modification,and antimicrobial mechanism.Thereby,this review will give an insight into the trends and challenges facing on this particular kind of antimicrobial materials. 展开更多
关键词 Antimicrobial peptides(AMPs) drug resistance Biomaterials Antimicrobial materials Antimicrobial mechanism
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