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.

尽管对分子水平的生命的理解已经发展上个世纪令人惊叹的速度，解决医疗问题的实用能力通过分子干预尚未以相同的速度发展。全球艾滋病毒流行病，以及我们无法有效治疗癌症，都证明了这一基本事实。的当然，有很多原因。人体是一台复杂的机器。我们可能列出了零件的列表，但是大多数零件的功能仍然是一个谜。重组 DNA技术，科学的突破，彻底改变了人类的研究疾病，还没有提供治疗疾病的一般处方。毒品是为此目的的主要工具以及时尚所需的合成有机化学今天他们与一个世纪前大致相同。最后，经济障碍与药物发现相关的是令人生畏的。该开拓者的提案解决了一项可以缩小基本之间差距的技术研究发现以及这种见解在医学上的应用。方法，称为“化学演化”（见下文），提供了将药物从巨大的合成小分子种群。它有可能改变药物从需要数百种化学师的过程中发现和大型制药公司，对有知识知识的研究生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具有学术界的良好往绩记录和行业。此外，我们最近的试点研究已经确定了进化的小分子[1-3]。这些研究是两种科学的主题，去年，化学和工程新闻中的技术评论文章，他们被评为2004年的“化学重点”（由美国化学关键化学进步学会）[4-6]。尽管它很大潜力和兴奋引起的，三个不同的联邦机构下降了为技术的进一步发展，理由是它太雄心勃勃太冒险了。