Preparation of 'side-chain-to-side-chain' cyclic peptides by Allyl and Alloc strategy: potential for library synthesis
Preparation of 'side-chain-to-side-chain' cyclic peptides by Allyl and Alloc strategy: potential for library synthesis
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DOI：
10.1111/j.1399-3011.2001.00816.x
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发表时间：
2001-03-01
期刊：
影响因子：
--
通讯作者：
Hruby, VJ
中科院分区：
文献类型：
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作者：
Grieco, P;Gitu, PM;Hruby, VJ
对侧链对侧链环肽制备中烯丙基/烯丙氧羰基（allyl/ Alloc）的自动和手动脱保护方法进行了评价。采用标准的烯丙基/Alloc脱保护方法，在自动肽合成仪上制备了一个含有内酰胺桥（7个氨基酸）的小环肽库。我们证明了在特定中性条件下去除烯丙基/Alloc保护基团的Guibe方法[Pd(PPh3)(4)/PhsiH(3))/DCM]是一种有用、有效和可靠的方法，可以在树脂上制备长环肽。我们还人工合成了含有24个氨基酸残基的环胰高血糖素类似物。这些结果表明，适当控制钯介导的烯丙基/Alloc保护基团的脱保护可以在树脂上使用自动肽合成器制备长链环肽。
Automated and manual deprotection methods for allyl/allyloxycarbonyl (Allyl/Alloc) were evaluated for the preparation of side-chain-to-side-chain cyclic peptides. Using a standard Allyl/Alloc deprotection method, a small library of cyclic peptides with lactam bridges (with seven amino acids) was prepared on an automatic peptide synthesizer. We demonstrate that the Guibe method for removing Allyl/Alloc protecting groups under specific neutral conditions [Pd(PPh3)(4)/PhsiH(3))/DCM] can be a useful, efficient and reliable method for preparing long cyclic peptides on a resin. We have also manually synthesized a cyclic glucagon analogue containing 24 amino acid residues. These results demonstrated that properly controlled palladium-mediated deprotection of Allyl/Alloc protecting groups can be used to prepare cyclic peptides on the resin using an automated peptide synthesizer and cyclic peptides with a long chain.