An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity.
An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity.
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DOI：
10.3791/54750
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发表时间：
2016-11-02
期刊：
影响因子：
--
通讯作者：
Cobb SL
中科院分区：
文献类型：
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作者：
Bolt HL;Denny PW;Cobb SL
该方案描述了含有两种不同官能化阳离子单体的线性类肽的手动固相合成。在该方法中，氨基官能化的“赖氨酸”和胍基官能化的“精氨酸”类肽单体可以包含在相同的类肽序列内。该程序使用树脂上（N-（1-（4，4-二甲基-2，6-二氧代亚环己基）乙基）或Dde保护，正交条件为赖氨酸单体的Boc保护。随后的脱保护允许有效的树脂上胍基化反应以形成精氨酸残基。该程序与常用的类肽合成的亚单体方法相容，允许使用常见的实验室设备和市售试剂制备简单的类肽。描述了两种混合类肽的代表性合成、纯化和表征。这些化合物作为潜在的抗感染药物的筛选试验对墨西哥利什曼原虫的评价也进行了描述。原生寄生虫L.墨西哥黑热病是皮肤利什曼病的病原体，这是一种被忽视的热带疾病，影响全世界多达1 200万人。
This protocol describes the manual solid-phase synthesis of linear peptoids that contain two differently functionalized cationic monomers. In this procedure amino functionalized 'lysine' and guanido functionalized 'arginine' peptoid monomers can be included within the same peptoid sequence. This procedure uses on-resin (N-(1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl) or Dde protection, orthogonal conditions to the Boc protection of lysine monomers. Subsequent deprotection allows an efficient on-resin guanidinylation reaction to form the arginine residues. The procedure is compatible with the commonly used submonomer method of peptoid synthesis, allowing simple peptoids to be made using common laboratory equipment and commercially available reagents. The representative synthesis, purification and characterization of two mixed peptoids is described. The evaluation of these compounds as potential anti-infectives in screening assays against Leishmania mexicana is also described. The protozoan parasite L. mexicana is a causative agent of cutaneous leishmaniasis, a neglected tropical disease that affects up to 12 million people worldwide.