Aqueous Synthesis of poly-beta-Peptides

描述(申请人提供)：β-氨基酸低聚体具有稳定的二级结构的发现引发了人们对这种多肽仿制药的合成、研究和应用的极大兴趣。然而，制备聚β-多肽的一些缺点包括使用大量摩尔过剩的昂贵偶联剂和多步骤。基于Jeffrey Bode教授实验室最近发现的酮酸-羟胺多肽连接反应，我们在水溶液条件下通过迭代、无试剂偶联异恶唑烷类单体合成了多β-多肽。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，这些单体已被证明是潜在有用的治疗药物，用于生物医学问题的管理。此外，我们希望使用我们目前的溶液相方法进行多β-肽的固相合成。此外，我们计划使用我们的异氧索利定方法合成β-肽，以制备HIV Tat DNA结合蛋白的β-肽类似物，并检测其与核酸或候选药物的结合。

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.