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Structural biology of cell-cycle proteins 细胞周期蛋白的结构生物学
Drug Discovery Today: TARGETS Pub Date : 2004-08-01 DOI: 10.1016/S1741-8372(04)02431-4
Sarah Major, Jane A Endicott
{"title":"Structural biology of cell-cycle proteins","authors":"Sarah Major,&nbsp;Jane A Endicott","doi":"10.1016/S1741-8372(04)02431-4","DOIUrl":"10.1016/S1741-8372(04)02431-4","url":null,"abstract":"<div><p>The master regulators of the eukaryotic cell cycle are cyclin-dependent protein kinases (CDKs), a highly conserved but functionally diverse enzyme family that also has essential roles in transcription, neuronal physiology, differentiation and apoptosis. CDK-containing complexes drive cell-cycle events and, as the targets of checkpoint pathways, integrate signals to ensure appropriate cell-cycle progression. X-ray crystallography has provided a detailed understanding of the mechanisms by which CDK activity is regulated. Recently reported structures have provided insights into how the protein assemblies that mediate the specific degradation of CDK regulatory proteins function and how checkpoint pathways integrate with the cell cycle.</p></div>","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"3 4","pages":"Pages 136-142"},"PeriodicalIF":0.0,"publicationDate":"2004-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1741-8372(04)02431-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85286786","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: 2
A surfeit of ‘-omics’ 过量的“经济学”
Drug Discovery Today: TARGETS Pub Date : 2004-08-01 DOI: 10.1016/S1741-8372(04)02434-X
Walter Blackstock
{"title":"A surfeit of ‘-omics’","authors":"Walter Blackstock","doi":"10.1016/S1741-8372(04)02434-X","DOIUrl":"10.1016/S1741-8372(04)02434-X","url":null,"abstract":"","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"3 4","pages":"Pages 125-127"},"PeriodicalIF":0.0,"publicationDate":"2004-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1741-8372(04)02434-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90101835","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: 1
Tethering in early target assessment 早期目标评估的束缚
Drug Discovery Today: TARGETS Pub Date : 2004-08-01 DOI: 10.1016/S1741-8372(04)02441-7
Johan D Oslob, Daniel A Erlanson
{"title":"Tethering in early target assessment","authors":"Johan D Oslob,&nbsp;Daniel A Erlanson","doi":"10.1016/S1741-8372(04)02441-7","DOIUrl":"10.1016/S1741-8372(04)02441-7","url":null,"abstract":"<div><p>The high cost of drug discovery and development requires that the validity and druggability of targets are assessed as early as possible. Protein–protein interactions are clinically important but are usually high-risk targets when pursuing small-molecule approaches. Therefore, early target assessment might be particularly valuable when small-molecule modulation of a member from this difficult class is being considered as a means for therapeutic intervention. In this article, we first review the principles behind a fragment-based drug discovery approach known as Tethering. We then illustrate how this technique, which was initially developed to find small-molecule hits for validated targets, can also be used in the early assessment of a protein–protein interaction as a target for small molecules.</p></div>","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"3 4","pages":"Pages 143-150"},"PeriodicalIF":0.0,"publicationDate":"2004-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1741-8372(04)02441-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74255666","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: 10
Developments in effective application of small inhibitory RNA (siRNA) technology in mammalian cells 小抑制RNA (siRNA)技术在哺乳动物细胞中的有效应用进展
Drug Discovery Today: TARGETS Pub Date : 2004-08-01 DOI: 10.1016/S1741-8372(04)02447-8
Benjamin G Cocks , Thomas P Theriault
{"title":"Developments in effective application of small inhibitory RNA (siRNA) technology in mammalian cells","authors":"Benjamin G Cocks ,&nbsp;Thomas P Theriault","doi":"10.1016/S1741-8372(04)02447-8","DOIUrl":"https://doi.org/10.1016/S1741-8372(04)02447-8","url":null,"abstract":"<div><p><span>siRNA technology provides a useful means of achieving reduction of gene expression in mammalian cells. In this article we focus on recent advances that make siRNA technology more practical as a tool for target validation. New advances include better use of sequence databases to assist in the design of reagents and improved diligence in the evaluation of target and off-target effects using appropriate controls and </span>gene expression microarrays. The new developments will allow progress in the evaluation of individual targets and target combinations and will enable comprehensive efforts to define mammalian cell processes.</p></div>","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"3 4","pages":"Pages 165-171"},"PeriodicalIF":0.0,"publicationDate":"2004-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1741-8372(04)02447-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91651560","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: 4
Carbohydrate arrays as tools for the glycomics revolution 碳水化合物阵列作为糖组学革命的工具
Drug Discovery Today: TARGETS Pub Date : 2004-08-01 DOI: 10.1016/S1741-8372(04)02443-0
Matthew D Disney, Peter H Seeberger
{"title":"Carbohydrate arrays as tools for the glycomics revolution","authors":"Matthew D Disney,&nbsp;Peter H Seeberger","doi":"10.1016/S1741-8372(04)02443-0","DOIUrl":"https://doi.org/10.1016/S1741-8372(04)02443-0","url":null,"abstract":"<div><p>Determining the roles of carbohydrates in cell biology is hindered by the tremendous efforts that must be taken either to synthesize carbohydrates chemically or to isolate them from natural sources. Several platforms have been developed to study glycobiology. These platforms include the covalent and non-covalent immobilization of carbohydrates on microtiter plates, nitrocellulose membranes, coated slides, glass slides, gold surfaces and microspheres. Each platform has both positive and negative attributes for studying carbohydrate biology, such as flexibility and the amount of material required for study. Here we discuss these techniques with the goal of developing a ‘gold standard’ in the field of glycomics.</p></div>","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"3 4","pages":"Pages 151-158"},"PeriodicalIF":0.0,"publicationDate":"2004-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1741-8372(04)02443-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91651561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 25
Metabolic syndrome: ‘the whole is greater than the sum of its parts’ 代谢综合征:“整体大于部分之和”
Drug Discovery Today: TARGETS Pub Date : 2004-08-01 DOI: 10.1016/S1741-8372(04)02442-9
Mirta Grifman
{"title":"Metabolic syndrome: ‘the whole is greater than the sum of its parts’","authors":"Mirta Grifman","doi":"10.1016/S1741-8372(04)02442-9","DOIUrl":"10.1016/S1741-8372(04)02442-9","url":null,"abstract":"","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"3 4","pages":"Pages 134-135"},"PeriodicalIF":0.0,"publicationDate":"2004-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1741-8372(04)02442-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91423151","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: 1
Carbohydrate arrays as tools for the glycomics revolution 碳水化合物阵列作为糖组学革命的工具
Drug Discovery Today: TARGETS Pub Date : 2004-08-01 DOI: 10.1016/S1741-8372(04)02443-0
M. Disney, P. Seeberger
{"title":"Carbohydrate arrays as tools for the glycomics revolution","authors":"M. Disney, P. Seeberger","doi":"10.1016/S1741-8372(04)02443-0","DOIUrl":"https://doi.org/10.1016/S1741-8372(04)02443-0","url":null,"abstract":"","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"55 1","pages":"151 - 158"},"PeriodicalIF":0.0,"publicationDate":"2004-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80432770","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: 24
Attacking amyloid fibres 攻击淀粉样纤维
Drug Discovery Today: TARGETS Pub Date : 2004-08-01 DOI: 10.1016/S1741-8372(04)02444-2
Jo Whelan
{"title":"Attacking amyloid fibres","authors":"Jo Whelan","doi":"10.1016/S1741-8372(04)02444-2","DOIUrl":"10.1016/S1741-8372(04)02444-2","url":null,"abstract":"","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"3 4","pages":"Page 128"},"PeriodicalIF":0.0,"publicationDate":"2004-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1741-8372(04)02444-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91255032","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
Developments in effective application of small inhibitory RNA (siRNA) technology in mammalian cells 小抑制RNA (siRNA)技术在哺乳动物细胞中的有效应用进展
Drug Discovery Today: TARGETS Pub Date : 2004-08-01 DOI: 10.1016/S1741-8372(04)02447-8
B. Cocks, T. Theriault
{"title":"Developments in effective application of small inhibitory RNA (siRNA) technology in mammalian cells","authors":"B. Cocks, T. Theriault","doi":"10.1016/S1741-8372(04)02447-8","DOIUrl":"https://doi.org/10.1016/S1741-8372(04)02447-8","url":null,"abstract":"","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"39 1","pages":"165-171"},"PeriodicalIF":0.0,"publicationDate":"2004-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85589593","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: 4
Allan Bradley discusses mice, men and genetics 艾伦·布拉德利讨论了老鼠、人类和遗传学
Drug Discovery Today: TARGETS Pub Date : 2004-08-01 DOI: 10.1016/S1741-8372(04)02446-6
Allan Bradley (Director) , Jayne V Carey (Interviewer), Samantha Barton (Interviewer)
{"title":"Allan Bradley discusses mice, men and genetics","authors":"Allan Bradley (Director) ,&nbsp;Jayne V Carey (Interviewer),&nbsp;Samantha Barton (Interviewer)","doi":"10.1016/S1741-8372(04)02446-6","DOIUrl":"10.1016/S1741-8372(04)02446-6","url":null,"abstract":"<div><p>Allan Bradley is one of the pioneers of embryonic stem cell technology and is world-renowned for his work on gene targeting. Allan started studying natural sciences at the University of Cambridge, UK, where he developed a strong interest for genetics. He stayed at Cambridge to complete his PhD studies and continued his post-doctorate research into mouse embryonic stem cells. In 1987, Allan left the UK to take up an assistant professorship position at Baylor College of Medicine, Texas, USA, and set up his own lab focusing on gene targeting. His expertise in genetics and in developing novel technologies led to his appointment as a Director of the Sanger Institute in 2000. Allan is an author of over 180 scientific publications, including his first paper on the creation of germline chimeras at the age of 24. Recently, Allan has been appointed as a Fellow of the Royal Society and Fellow of the Academy of Medical Sciences.</p></div>","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"3 4","pages":"Pages 130-133"},"PeriodicalIF":0.0,"publicationDate":"2004-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1741-8372(04)02446-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78987213","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
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