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NIH Director's Pioneer Award

NIH 院长先锋奖

基本信息

批准号：
7683181
负责人：
PEHR A HARBURY
金额：
$ 76.17万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-30 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7683181
关键词：
Academia Acute Lymphocytic Leukemia Address Adopted Advisory Committees Affinity Affinity Chromatography Algorithms American Amino Acid Sequence Amino Acids Animal Model Antibodies Anticodon Arts Asthma Attributes of Chemicals Australia Award Basic Science Basophils Binding Biochemistry Biological Biological Availability Biological Factors Biopolymers Blast Phase Breeding CC chemokine receptor 3 California Cell Membrane Permeability Cells Chemical Engineering Chemical Evolution Chemicals Chemistry Chicago Clinic Clinical Trials Code Collaborations Collection Color Commit Communities Complex Coupled Crystallography Cysteine Cytoskeletal Filaments DNA Data Dengue Dengue Virus Deuterium Development Discipline of Nursing Disease Doctor of Medicine Doctor of Philosophy Drops Drug Prescriptions Drug resistance Economics Education Electrostatics Employment Engineering Environment Enzymes Eosinophilia Equilibrium Europe Evolution Expenditure Federal Government Figs - dietary Floods Freedom Funding Generations Genes Genetic Code Gleevec Goals Growth Human Human Resources Hydrogen Image In Vitro Individual Industry Infection Institutes Institution Interferon Receptor Interferons Journals Kilogram Kinetics Knockout Mice Knowledge Knowledge acquisition Laboratories Lead Learning Left Leucine Enkephalin Libraries Ligand Binding Ligands Location Maps Massachusetts Measurement Measures Medical Research Medicine Membrane Metabolic Methods Modeling Modification Molecular Molecular Biology Monitor Mus Myelogenous NMR Spectroscopy NS2-3 protease Names Nature Nucleic Acids Oral Organic Chemistry Organic Synthesis Pathway interactions Patients Peptide Nucleic Acids Peptide Sequence Determination Peptide aptamers Peptides Persons Phage Display Pharmaceutical Preparations Pharmacologic Substance Phase Phosphotransferases Physiology Pilot Projects Plasmids Polyribosomes Polystyrenes Population Positioning Attribute Positron-Emission Tomography Postdoctoral Fellow Price Primates Principal Investigator Probability Problem Solving Process Professional Education Property Protease Inhibitor Protein Footprinting Protein Tyrosine Kinase Proteins Protons Publications RNA Reaction Reagent Records Research Research Infrastructure Research Personnel Resistance Resolution Resources Rotation Route Running SCID Mice Scheme Science Scientist Screening for cancer Screening procedure Secure Series Shapes Signal Transduction Societies Solid Solvents Specificity Speed Staging Structure Students System T-Cell Receptor Techniques Technology Test Result Testing Therapeutic Translating Translation Process Translations Triose-Phosphate Isomerase Trust Tube Tyrosine United States United States National Institutes of Health Universities Variant Vertebral column Work Zebrafish airway hyperresponsiveness anticancer research aptamer base catalyst cell type combinatorial chemistry cost design drug development drug discovery empowered eosinophil eotaxin receptor experience falls genetic manipulation graduate student high risk high throughput screening inhibitor/antagonist insight interleukin-5 receptor kinase inhibitor knowledge base leukemia macromolecule medical schools millisecond molecular mechanics molecular recognition mouse model mutant new technology news novel olfactory receptor post-doctoral training pre-clinical professor programs protein protein interaction protein structure receptor research and development routine practice sensor small molecule structural biology technology development three dimensional structure tool trend

项目摘要

While the understanding of life at the molecular level has advanced with breathtaking speed over the last century, a practical ability to solve medical problems through molecular intervention has not developed at the same pace. The global HIV epidemic, and our inability to effectively treat cancer, both evince this basic fact. Of course, there are many reasons for this. The human body is a complex machine. We may have a list of the parts, but the function of most of them remains a mystery. Recombinant DNA technology, the scientific breakthrough that revolutionized the study of human disease, has not also provided a general prescription for treating disease. Drugs are the primary tools for this purpose, and the synthetic organic chemistry required to fashion them today is much the same as it was a century ago. Finally, the economic hurdles associated with drug discovery are daunting. This Pioneer proposal addresses a technology that can close the gap between basic research discoveries, and the application of such insights to medicine. The approach, called "chemical evolution" (see below), provides the means to breed drugs out of enormous synthetic small-molecule populations. It has the potential to transform drug discovery from a process requiring hundreds of chemist-years and the infrastructure of a large pharmaceutical company, to something a graduate student with knowledge of basic molecular biology can accomplish in a month. Chemical evolution is closely related to nucleic-acid and protein evolution techniques with proven track records in academia and industry. Moreover, our recent pilot studies have definitively established the feasibility of evolving small molecules[1-3]. These studies were the subject of two Science and Technology review articles in Chemical and Engineering News over the last year, and they were named a "Chemistry Highlight" for 2004 (a short annual compilation by the American Chemical Society of key advances in chemistry)[4-6]. Despite its enormous potential and the excitement it engenders, three different federal agencies have declined to fund further development of the technology on the grounds that it is too ambitious and too risky.

虽然在分子水平上对生命的理解随着以惊人的速度跨越上个世纪，具有解决医疗问题的实际能力并没有以同样的速度发展。全球艾滋病毒流行病，以及我们无法有效治疗癌症，都表明了这一基本事实。的当然，这是有很多原因的。人体是一台复杂的机器。我们可能我有一个零件清单，但其中大部分的功能仍然是个谜。重组 DNA技术是一项科学突破，它彻底改变了人类的研究。疾病，也没有提供治疗疾病的通用处方。毒品是这一目的的主要工具，以及时尚所需的合成有机化学他们今天和世纪前差不多。最后，经济障碍与药物发现相关的问题令人生畏。这项先锋计划提出了一项技术，可以缩小差距研究发现，以及这些见解在医学上的应用。方法，称为“化学进化”（见下文），提供了从药物中繁殖药物的方法。巨大的合成小分子群体。它有潜力将药物从一个需要数百个化学家年和基础设施的过程中发现大型制药公司，以东西一个研究生的基本知识分子生物学可以在一个月内完成化学演化与核酸和蛋白质进化技术在学术界有着良好的记录，行业此外，我们最近的试验性研究已明确确定了以下做法的可行性：进化小分子[1-3]。这些研究是两个科学和去年《化学与工程新闻》上的技术评论文章，它们被命名为2004年的“化学亮点”（由美国化学学会（American Chemical Society of Key Advances in Chemistry）[4-6]。尽管其巨大的潜力和它所带来的兴奋，三个不同的联邦机构已经拒绝了资助这项技术的进一步发展，理由是它过于雄心勃勃，太冒险了