Peptide Head‐to‐Tail Cyclization: A “Molecular Claw” Approach
Peptide Head‐to‐Tail Cyclization: A “Molecular Claw” Approach
复制标题
肽头尾环化：“分子爪”方法
DOI：
10.1002/ejoc.202100185
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
K.
中科院分区：
文献类型：
--
作者：
Yamagami;S.; Okada;Y.; Kitano;Y.; Chiba;K.
天然环肽和人工环肽由于其酶的稳定性、细胞通透性和药理活性都比线性环肽具有更高的稳定性和药理活性，因此在治疗上有着广泛的应用前景。最简单但最具挑战性的环化反应是头到尾的环化方式，其中线性多肽通过C-末端和N-末端环化，因为目前大多数多肽合成一直被C-末端保护载体的使用所主导。在这里，我们证明了可溶性标签辅助的多肽合成与主链酰胺连接子策略相结合的方法适用于头尾环化反应。使用酰胺“N-标签”而不是一般的末端C-标签能够在支撑物上实现有效的头尾环化。成功环化的关键是能够抓住多肽中心的标记位置。
Both naturally occurring and artificial cyclic peptides are in high demand for a wide range of therapeutic applications due to the improvement of their enzymatic stability, cell permeability, and pharmacological activity compared to their linear counterparts. Among the simplest yet challenging cyclizations is the head‐to‐tail fashion, where linear peptides are cyclized via C‐ and N‐termini, since most current peptide synthesis has been dominated by the use of C‐terminal protecting supports. Herein, we demonstrate that a soluble‐tag‐assisted liquid‐phase peptide synthesis in combination with a backbone amide linker strategy is applicable to the head‐to‐tail cyclization. The use of an amide “N‐tag” instead of the general terminal C‐tag enables an effective head‐to‐tail cyclization on‐support. The key for successful cyclization is a tagging position that enables the center of the peptide to be grabbed.