Department of Chemistry, Institute for Genomics and Systems Biology, The University of Chicago, Chicago, IL, USA.
Methods Mol Biol. 2022;2371:159-174. doi: 10.1007/978-1-0716-1689-5_9.
Macrocyclization can confer enhanced stability, target affinity, and membrane permeability to peptide scaffolds, all of which are desirable properties for chemical probes and therapeutics. A wide array of macrocyclization chemistries have been reported over the last few decades; however, these often have limited compatibility with each other and across chemical environments, thus restricting access to specific molecular properties. In an effort to address some of these limitations, we recently described the use of Diels-Alder [4 + 2] cycloadditions for peptide macrocyclization. Among the attributes of this chemistry, we demonstrated that Diels-Alder cyclization can template diverse peptide secondary structures, proceed in organic or aqueous environments, and endow improved pharmacologic properties on cyclized peptides. Here, we present synthetic processes and characterization methods for the synthesis of Diels-Alder cyclized peptides.
环化可以赋予肽支架更高的稳定性、靶亲和力和膜通透性，这些都是化学探针和治疗剂所需的理想特性。在过去几十年中，已经报道了多种环化化学方法;然而，这些方法通常彼此之间以及在化学环境中都具有有限的兼容性，从而限制了对特定分子性质的获取。为了克服其中的一些限制，我们最近描述了使用 Diels-Alder [4 + 2] 环加成反应进行肽环化。在这种化学方法中，我们证明了 Diels-Alder 环化可以模板化不同的肽二级结构，在有机或水相环境中进行，并且赋予环化肽改善的药理性质。在这里，我们提出了 Diels-Alder 环化肽的合成工艺和表征方法。
