Aqueous Synthesis of poly-beta-Peptides

描述（由申请人提供）：β -氨基酸低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，多肽制备的一些缺点包括使用大摩尔过量的昂贵偶联试剂和多步骤。基于Jeffrey Bode教授实验室最近发现的酮酸-羟胺肽连接，我们在水条件下通过迭代，试剂少偶联的异恶唑烷单体合成了多肽。我们的长期计划是利用我们的方法合成其他种类的异恶唑烷单体，包括环β肽，这些单体已被证明是生物医学问题管理的潜在有用的治疗剂。此外，我们希望使用我们目前的固相方法进行多肽的固相合成。此外，我们计划使用我们的异索烷方法合成β肽，以制备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性。

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.