Synthesis of a Chloroalkene Dipeptide Isostere-Containing Peptidomimetic and Its Biological Application
Synthesis of a Chloroalkene Dipeptide Isostere-Containing Peptidomimetic and Its Biological Application
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DOI：
10.1021/acsmedchemlett.7b00234
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发表时间：
2018-01-01
影响因子：
4.2
通讯作者：
Tamamura, Hirokazu
中科院分区：
文献类型：
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作者：
Kobayakawa, Takuya;Matsuzaki, Yudai;Tamamura, Hirokazu
据报道，首次快速有效地化学合成了含有氯烯二肽电子等排体 (CADI) 的环状精氨酸-甘氨酸-天冬氨酸 (RGD) 肽。通过开发的合成方法，以非对映选择性烯丙基烷基化为关键反应，得到了 N-叔丁基磺酰基保护的 CADI。该 CADI 还通过几个步骤转化为 N-Fmoc 保护的 CADI。 CADI 用于基于 Fmoc 的固相肽合成。首次合成含有 CADI 的环状 RGD 肽获得成功，并且发现合成的含有 CADI 的拟肽比母体环肽是更有效的针对整合素介导的细胞附着的抑制剂。
The first rapid and efficient chemical synthesis of a cyclic Arg-Gly-Asp (RGD) peptide containing a chloroalkene dipeptide isostere (CADI) is reported. By a developed synthetic method, an N-tert-butylsulfonyl protected CADI was obtained utilizing diastereoselective allylic alkylation as a key reaction. This CADI was also transformed into an N-Fmoc protected CADI in a few steps. The CADI was used in Fmoc-based solid-phase peptide synthesis. The first synthesis of a CADI-containing cyclic RGD peptide was successful, and the synthesized CADI-containing peptidomimetic was found to be a more potent inhibitor against integrin-mediated cell attachment than the parent cyclic peptide.