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Automated Protein Crystal Growth in Lipidic Cubic Phase

脂质立方相中的自动化蛋白质晶体生长

基本信息

批准号：
6485387
负责人：
PETER K NOLLERT-VON SPECHT
金额：
$ 13.9万
依托单位：
EMERALD BIOSTRUCTURES
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-03-15 至 2003-09-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6485387
关键词：
biomedical automation biotechnology crystallization high throughput technology lipid bilayer membrane liquid crystal membrane proteins method development physical property

项目摘要

Information derived from the three-dimensional structure of proteins has been of increasing importance in the development of pharmaceuticals. Structures determined using 3-D X-ray crystallography have been vital in the development of anti-AIDS and anti-cancer agents. Membrane proteins constitute a large fraction of genes, and are the target of approximately 60% of the drugs on the market. Determinations of the 3-D structures of membrane proteins have lagged far behind the determination of structures of soluble proteins. One technique recently developed for membrane protein crystal growth has been the use of lipidic cubic phase (LCP) materials in which the membrane protein crystallizes in a microenvironment resembling native lipid bilayer. One difficulty in working with these materials is the extreme viscosity of the LCP-protein mixture. Conventional methods of dispensing LCP materials using a syringe have been developed, but automating filling and dispensing of this high-viscosity material from a syringe has been challenging, and new methods for LCP-based crystal growth under development require contact-free dispensation of LCP onto substrate. The goal of this project is to develop an innovative method for contact-free dispensation of LCP onto a substrate, allowing membrane protein crystal growth to be automated in a high-throughput manner. PROPOSED COMMERCIAL APPLICATION: Our proposed project will facilitate the determination of membrane protein structures. Any technology developed to speed the determination of these structures would be of great value in developing novel pharmacuticafs. Emerald is the exclusive licensee of the LCP technology developed at UCSF. Emerald BioStructures has employed three crystallographers with membrane protein experience, Craig Behnke, Thomas Richter, and Peter Nollert, one of the developers of LCP technology at UCSF.

从蛋白质的三维结构中获得的信息在药物开发中越来越重要。使用三维X射线晶体学确定的结构在抗艾滋病和抗癌药物的开发中至关重要。膜蛋白构成基因的很大一部分，并且是市场上大约60%的药物的靶标。膜蛋白三维结构的测定远远落后于可溶性蛋白结构的测定。最近开发的一种用于膜蛋白晶体生长的技术是使用介晶立方相（LCP）材料，其中膜蛋白在类似于天然脂质双层的微环境中结晶。使用这些材料的一个困难是LCP-蛋白质混合物的极端粘度。已经开发了使用注射器分配LCP材料的常规方法，但是从注射器自动填充和分配这种高粘度材料具有挑战性，并且正在开发的基于LCP的晶体生长的新方法需要将LCP无接触地分配到衬底上。该项目的目标是开发一种创新的方法，用于将LCP无接触分配到基底上，使膜蛋白晶体生长以高通量的方式自动化。建议的商业应用：我们建议的项目将促进膜蛋白结构的测定。任何技术的发展，以加快确定这些结构将是非常有价值的开发新的pharmacuticafs。Emerald是UCSF开发的LCP技术的独家许可证。Emerald BioStructures聘请了三位具有膜蛋白经验的晶体学家，他们是克雷格·本克、托马斯·里希特和加州大学旧金山分校LCP技术的开发者之一彼得·诺勒特。