PEPTOIDS - A MODULAR APPROACH TO DRUG DISCOVERY
PEPTOIDS - A MODULAR APPROACH TO DRUG DISCOVERY
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DOI：
10.1073/pnas.89.20.9367
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发表时间：
1992-10-15
影响因子：
11.1
通讯作者：
BARTLETT, PA
中科院分区：
文献类型：
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作者：
SIMON, RJ;KANIA, RS;BARTLETT, PA
类肽是N-取代甘氨酸的低聚体，被描述为产生化学上不同的新分子文库的基序。计算了Ramachandran类型的曲线图，表明类肽的构象状态比多肽具有更大的构象多样性。这些单体含有叔丁基侧链和9-荧甲氧基甲氧基α-胺保护。用benzotriazol-1-yloxytris(pyrrolidino)phosphonium六氟磷酸盐或溴三(吡咯烷)六氟磷酸膦原位活化，人工和机器人控制类肽单体的齐聚反应。其他步骤与使用α-(9-荧甲氧基甲氧基)氨基酸合成多肽相同。共描述了15种单体和10种低聚物(类肽)。提供了具有代表性的寡肽对酶解的稳定性的初步数据。三个生物系统(牛胰腺α-淀粉酶、甲型肝炎病毒3C蛋白酶和人类免疫缺陷病毒反式激活反应元件RNA)的多肽配体的类肽版本与相应的多肽具有相似的亲和力。讨论了这些化合物的文库在基于受体或酶的分析中的潜在用途。
Peptoids, oligomers of N-substituted glycines, are described as a motif for the generation of chemically diverse libraries of novel molecules. Ramachandran-type plots were calculated and indicate a greater diversity of conformational states available for peptoids than for peptides. The monomers incorporate t-butyl-based side-chain and 9-fluorenylmethoxy-carbonyl alpha-amine protection. The controlled oligomerization of the peptoid monomers was performed manually and robotically with in situ activation by either benzotriazol-1-yloxytris(pyrrolidino)phosphonium hexafluorophosphate or bromotris(pyrrolidino)phosphonium hexafluorophosphate. Other steps were identical to peptide synthesis using alpha-(9-fluorenylmethoxycarbonyl)amino acids. A total of 15 monomers and 10 oligomers (peptoids) are described. Preliminary data are presented on the stability of a representative oligopeptoid to enzymatic hydrolysis. Peptoid versions of peptide ligands of three biological systems (bovine pancreatic alpha-amylase, hepatitis A virus 3C proteinase, and human immunodeficiency virus transactivator-responsive element RNA) were found with affinities comparable to those of the corresponding peptides. The potential use of libraries of these compounds in receptor- or enzyme-based assays is discussed.