Aqueous Synthesis of poly-beta-Peptides

聚-β-肽的水相合成

• 批准号: 7282499
• 负责人: Nancy Carrillo
• 金额: $ 3.09万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7282499
• 关键词: Adopted; Amino Acids; Chemistry; Class; Condition; Coupling; DNA-Binding Proteins; HIV; Keto Acids; Laboratories; Ligation; Methodology; Methods; Nucleic Acids; Peptide Synthesis; Peptides; Pharmaceutical Preparations; Phase; Polymers; Preparation; Reaction; Reagent; S Phase; Side; Solid; Solubility; Solutions; Structure; Therapeutic; Therapeutic Agents; aqueous; base; design; innovation; interest; monomer; peptide analog; peptidomimetics; polypeptide

DESCRIPTION (provided by applicant): The discovery that oligomers of beta-amino acids adopt stable secondary structures has sparked immense interest in the synthesis, study and application of this peptidomimetics. However, some of the drawbacks on the preparation of poly-beta-peptides include the use of large molar excesses of expensive coupling reagents and multiple steps. Based on the recently developed ketoacid-hydroxyamine peptide ligation discovered by the laboratories of Prof. Jeffrey Bode, we have synthesized poly-beta-peptides by iterative, reagent less coupling of isoxazolidines monomers under aqueous conditions. Our long term plan is to synthesis using our methodology, other classes of isoxazolidine monomers including cyclic-beta-peptides which, have shown to be potentially useful as therapeutic agents for the management of biomedical problems. Furthermore, we hope to perform solid phase synthesis of poly-beta-peptides using our current solution phase methodology. In addition, we plan to use our isoxasolidine approach to beta-peptide synthesis to prepare the beta-peptide analogue of the HIV Tat DNA binding protein and examine its attachment to nucleic acids or drug candidates.

描述（由申请人提供）：β-氨基酸寡聚物采用稳定的二级结构的发现引起了人们对这种肽模拟物的合成、研究和应用的极大兴趣。 然而，制备聚-β-肽的一些缺点包括使用大摩尔过量的昂贵偶联试剂和多个步骤。 基于 Jeffrey Bode 教授实验室最近开发的酮酸-羟胺肽连接技术，我们在水性条件下通过异恶唑烷单体的迭代、无试剂偶联合成了聚-β-肽。 我们的长期计划是使用我们的方法合成其他类别的异恶唑烷单体，包括环-β-肽，这些单体已被证明可用作治疗生物医学问题的治疗剂。 此外，我们希望使用我们当前的溶液相方法进行聚-β-肽的固相合成。 此外，我们计划使用 isoxasolidine 方法进行 β 肽合成，制备 HIV Tat DNA 结合蛋白的 β 肽类似物，并检查其与核酸或候选药物的附着情况。