Studies in Amide and Peptide Synthesis

酰胺和肽合成研究

基本信息

批准号：
10080734
负责人：
Jeffrey Nicholas Johnston
金额：
$ 34.39万
依托单位：
VANDERBILT UNIVERSITY
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：
2002-03-01 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10080734
关键词：
Adopted Amides Amidines Amines Amino Acids Benchmarking Biological Calorimetry Carbon Carboxylic Acids Catalysis Chemicals Complement Complex Cyclic Peptides Development Esters Evolution Excision Expeditions Foundations Glycine Goals Halogens Health Human Hydrogen Peroxide Hydroxylamine In Situ Ions Keto Acids Laboratories Life Ligation Methods Molecular Weight Names Natural Products Nature Nitrogen Nitrogen Dioxide Nylons Organic Chemistry Outcome Oxazoles Peptide Synthesis Peptides Pharmacologic Substance Phase Physical condensation Preparation Process Pyrrolidines Reaction Reaction Time Reagent Reporting Research Personnel Scheme Site Solid Source Speed Stereoisomer Techniques Technology Therapeutic Therapeutic Uses Titrations Triazoles Tryptophan Tyrosine Urea Water alkalinity base chemical synthesis cost drug development epimerization improved innovation interest nitroalkane novel strategies peptide chemical synthesis programs small molecule tool

项目摘要

4.2.1 Project Summary and Relevance This proposal seeks support to develop a fundamentally new approach to amide and peptide chemical synthesis, one that complements existing methods based on dehydrative amide synthesis using carboxylic acids and amines. Bromonitroalkanes serve as carboxylic acid surrogates in a direct amide synthesis that utilizes an amine acceptor and an activating agent (a halonium ion). The concise preparation of amides derived from nonnatural amino acids, common constituents of biologically active linear and cyclic peptides that have been isolated from natural sources, is a central theme. Without this new paradigm, alternative chemical methods would provide access to the desired amides at rising cost due to the large number of steps required to prepare complex peptides, and the contamination of intermediates and products by stereoisomers that are difficult to remove. The practical chemical synthesis of biologically active peptides is an immediate goal. In the short term, peptides of modest size (~10 residues) will be prepared and diversified. In the long term, this innovative approach to amide synthesis will be used in combination with conventional methods to provide access to large peptides (e.g. biologics) modified site-specifically with nonnatural amino acids.

4.2.1项目摘要和相关性该提案寻求支持以开发一种从根本上开始的酰胺和肽化学方法合成，一种使用基于脱水酰胺合成的现有方法的合成羧酸和胺。在直接酰胺的利用胺受体和激活剂（halonium离子）的合成。简洁源自非天然氨基酸的酰胺的制备，这是生物活性的常见成分从天然来源隔离的线性和环状肽是一个中心主题。没有这个新的范式，替代化学方法将以上升的成本提供对所需酰胺的访问由于制备复杂肽所需的大量步骤，并且污染立体异构体的中间体和产品难以删除。生物活性肽的实际化学合成是一个直接目标。在短期内尺寸适中（约10个残基）的肽将准备和多样化。从长远来看，这种创新酰胺合成方法将与常规方法结合使用以提供访问与非天然氨基酸特异性修饰的大型肽（例如生物制剂）。