Tryptophan in Multicomponent Petasis Reactions for Peptide Stapling and Late-Stage Functionalisation.
Tryptophan in Multicomponent Petasis Reactions for Peptide Stapling and Late-Stage Functionalisation.
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用于肽缝合和后期功能化的多组分 Petasis 反应中的色氨酸。
DOI：
10.1002/anie.202307782
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Krajcovicova S
中科院分区：
文献类型：
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作者：
Krajcovicova S
肽钉合是用于产生酶促稳定的大环肽的稳健策略。将生物相关标签（如细胞穿透基序或荧光染料）掺入肽中，同时保留其结合相互作用并增强其稳定性，这是非常受欢迎的。尽管色氨酸的吲哚支架为靶向功能化提供了独特的机会，但与其他氨基酸相比，其在肽钉合中的利用受到限制。在此，我们提出了一种使用色氨酸介导的Petasis反应进行肽钉合的方法。该方法能够合成钉合肽和标记肽，适用于溶液和固相合成。重要的是，Petasis反应与色氨酸的组合使用促进了以简单的多组分方式形成钉合肽，同时避免了不期望的副产物的形成。此外，这种方法允许有效和多样化的后期肽修饰，从而能够快速生产用于生物和医学应用的多种缀合物。
Peptide stapling is a robust strategy for generating enzymatically stable, macrocyclic peptides. The incorporation of biologically relevant tags (such as cell‐penetrating motifs or fluorescent dyes) into peptides, while preserving their binding interactions and enhancing their stability, is highly sought after. Despite the unique opportunities offered by tryptophan‘s indole scaffold for targeted functionalisation, its utilisation in peptide stapling has been limited as compared to other amino acids. Herein, we present an approach for peptide stapling using the tryptophan‐mediated Petasis reaction. This method enables the synthesis of both stapled and labelled peptides and is applicable to both solution and solid‐phase synthesis. Importantly, the use of the Petasis reaction in combination with tryptophan facilitates the formation of stapled peptides in a straightforward, multicomponent fashion, while circumventing the formation of undesired by‐products. Furthermore, this approach allows for efficient and diverse late‐stage peptide modifications, thereby enabling rapid production of numerous conjugates for biological and medicinal applications.