Incorporation of unprotected heterocyclic side chains into peptoid oligomers via solid-phase submonomer synthesis
Incorporation of unprotected heterocyclic side chains into peptoid oligomers via solid-phase submonomer synthesis
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DOI：
10.1021/ja0352101
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发表时间：
2003-07-23
影响因子：
15
通讯作者：
Zuckermann, RN
中科院分区：
文献类型：
--
作者：
Burkoth, TS;Fafarman, AT;Zuckermann, RN
肽类（n -取代甘氨酸）是一类重要的仿生低聚物，近年来在组合药物发现、基因治疗、药物传递和生物聚合物折叠等领域产生了重大影响。序列特异性肽类低聚物很容易由伯胺通过固相亚单体方法组装。然而，大多数在侧链中含有杂环氮的胺不能有效地结合。我们在这里提出了一种直接修正的亚单体方法，可以有效地将无保护的咪唑、吡啶、吡嗪、吲哚和喹啉纳入到长度长达15个单体的低聚物中。这种改进的方法在单体加成循环的酰化步骤中使用氯乙酸代替溴乙酸，并允许加入新的侧链，从而能够合成具有全新性质的类肽。
Peptoids (N-substituted glycines) are an important class of biomimetic oligomers that have made a significant impact in the areas of combinatorial drug discovery, gene therapy, drug delivery, and biopolymer folding in recent years. Sequence-specific peptoid oligomers are easily assembled from primary amines by the solid-phase submonomer method. However, most amines that contain heterocyclic nitrogens in the side chain do not incorporate efficiently. We present here a straightforward revision of the submonomer method that allows efficient incorporation of unprotected imidazoles, pyridines, pyrazines, indoles, and quinolines into oligomers as long as 15 monomers in length. This improved method uses chloroacetic acid instead of bromoacetic acid in the acylation step of the monomer addition cycle, and allows for the incorporation of new side chains that should enable the synthesis of peptoids with entirely new properties.