Institute for Organic and Biomolecular Chemistry, University of Göttingen, Tammannstrasse 2, D-37077 Göttingen, Germany.
Beilstein J Org Chem. 2012;8:1576-83. doi: 10.3762/bjoc.8.180. Epub 2012 Sep 19.
The concept of template-assembled synthetic proteins (TASP) describes a central scaffold that predefines the three dimensional structure for diverse molecules linked to this platform. Cyclic β-tripeptides are interesting candidates for use as templates due to their conformationally defined structure, stability to enzymatic degradation, and ability to form intermolecular stacked tubular structures. To validate the applicability of cyclic β-tripeptides within the TASP concept, an efficient synthesis of the cyclopeptide with orthogonal functionalization of the side chains is desired. A solid-phase-supported route with on-resin cyclization is described, employing the aryl hydrazide linker cleavable by oxidation. An orthogonal protection-group strategy allows functionalization of the central cyclic β-tripeptide with up to three different peptide fragments or fluorescent labels.
模板组装合成蛋白（TASP）的概念描述了一个中央支架，为连接到该平台的各种分子预先定义了三维结构。由于其结构确定的构象、对酶降解的稳定性以及形成分子间堆叠管状结构的能力，环状 β-三肽是用作模板的有趣候选物。为了验证环状 β-三肽在 TASP 概念中的适用性，需要高效合成具有侧链正交官能化的环肽。本文描述了一种使用氧化可裂解的芳基腙连接基的固相结合的方法，该方法可以在树脂上进行环化。正交保护基策略允许用多达三个不同的肽片段或荧光标记物对中央环状 β-三肽进行官能化。
