Aqueous Synthesis of poly-beta-Peptides

描述（由申请人提供）：发现β-氨基酸的寡聚体具有稳定的二级结构，这一发现引发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，我们通过异恶唑烷单体在水性条件下的迭代、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，包括环状β-肽，其已显示出潜在地可用作用于管理生物医学问题的治疗剂。 此外，我们希望使用我们目前的溶液相方法进行多聚β肽的固相合成。 此外，我们计划使用我们的isoxasolidine方法来合成β-肽，以制备HIV达特DNA结合蛋白的β-肽类似物，并检查其与核酸或候选药物的连接。

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.