A Systematic Approach to the Chemical Synthesis (RMI)

化学合成 (RMI) 的系统方法

• 批准号: 7265325
• 负责人: STEPHEN B.H. KENT
• 金额: $ 26.78万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-23 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7265325
• 关键词: Address; Amino Acid Sequence; Arts; Biology; Biomedical Research; CCR5 gene; Chemicals; Chemistry; Chemokine (C-C Motif) Receptor 5; Class; Classification; Clinical; Communicable Diseases; Complex; Condition; Crystallization; Drug Design; G Protein-Coupled Receptor Genes; G-Protein-Coupled Receptors; GTP-Binding Proteins; Goals; Human; In Vitro; Inflammation; Integral Membrane Protein; Knowledge; Lead; Length; Ligands; Lipid Bilayers; Measures; Membrane Proteins; Methods; Molecular; Molecular Biology; Nervous system structure; Operative Surgical Procedures; Opioid Receptor; Pain management; Peptides; Pliability; Positioning Attribute; Preparation; Production; Protein Biosynthesis; Proteins; Research; Research Personnel; Resolution; Resources; Route; Structure; Structure-Activity Relationship; Synthesis Chemistry; chemical synthesis; chemokine receptor; clinically relevant; peptide chemical synthesis; polypeptide; programs; protein function; protein structure; receptor; reconstitution; structural biology; tool

DESCRIPTION (provided by applicant): Polytopic helical integral membrane proteins are an important class of proteins that have been understudied because of technical issues regarding their expression, purification, and crystallization. Total chemical protein synthesis represents a potential route to these important proteins, but is currently hampered by insolubility of the transmembrane peptides required for protein assembly. To address this issue, we propose to develop a general method to render transmembrane peptides soluble for the manipulations necessary in chemical protein synthesis. We will then synthesize a 7 TM integral membrane protein to demonstrate the viability of chemical membrane protein synthesis. Establishing routine synthetic access to integral membrane proteins will provide tools to study their mechanisms in detail not currently available to molecular biology, which will eventually lead to a better understanding of how these proteins function in normal and pathological states.

描述(申请人提供)：多位螺旋整合膜蛋白是一类重要的蛋白质，由于其表达、纯化和结晶的技术问题，一直未得到充分的研究。总的化学蛋白质合成是获得这些重要蛋白质的潜在途径，但目前由于蛋白质组装所需的跨膜肽的不溶性而受到阻碍。为了解决这个问题，我们建议开发一种通用的方法来使跨膜多肽可溶于化学蛋白质合成中所需的操作。然后，我们将合成一个7TM完整的膜蛋白，以证明化学膜蛋白合成的可行性。建立对完整膜蛋白的常规合成途径将为详细研究其机制提供分子生物学目前尚不具备的工具，这最终将导致更好地理解这些蛋白在正常和病理状态下的功能。