School of Food and Biological Engineering, Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, Hefei 230009, China.
Org Biomol Chem. 2024 May 8;22(18):3584-3588. doi: 10.1039/d4ob00472h.
Asp-based lactam cyclic peptides are considered promising drug candidates. However, using Fmoc solid-phase peptide synthesis (Fmoc-SPPS) for these peptides also causes aspartimide formation, resulting in low yields or even failure to obtain the target peptides. Here, we developed a diaminodiacid containing an amide bond as a β-carboxyl-protecting group for Asp to avoid aspartimide formation. The practicality of this diaminodiacid has been illustrated by the synthesis of lactam cyclic peptide cyclo[Lys9,Asp13] KIIIA7-14 and 1Y.
基于天冬氨酸的内酰胺环肽被认为是很有前途的药物候选物。然而，使用 Fmoc 固相肽合成（Fmoc-SPPS）来合成这些肽也会导致天冬酰胺亚胺的形成，从而导致产率低，甚至无法获得目标肽。在这里，我们开发了一种含有酰胺键的二氨基二酸作为 Asp 的β-羧基保护基，以避免天冬酰胺亚胺的形成。通过合成内酰胺环肽环[Lys9,Asp13] KIIIA7-14 和 1Y，说明了这种二氨基二酸的实用性。
