Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.
J Pept Sci. 2010 Apr;16(4):178-85. doi: 10.1002/psc.1218.
Cyclization of bioactive peptides, utilizing functional groups serving as natural pharmacophors, is often accompanied with loss of activity. The backbone cyclization approach was developed to overcome this limitation and enhance pharmacological properties. Backbone cyclic peptides are prepared by the incorporation of special building units, capable of forming amide, disulfide and coordinative bonds. Urea bridge is often used for the preparation of cyclic peptides by connecting two amine functionalized side chains. Here we present urea backbone cyclization as an additional method for the preparation of backbone cyclic peptide libraries. A straightforward method for the synthesis of crystalline Fmoc-N(alpha) [omega-amino(Alloc)-alkyl] glycine building units is presented. A set of urea backbone cyclic Glycogen Synthase Kinase 3 analogs was prepared and assessed for protein kinase B inhibition as anticancer leads.
生物活性肽的环化作用，利用作为天然药效团的官能团，通常伴随着活性的丧失。为了克服这一限制并增强药理性质，开发了骨干环肽方法。骨干环肽是通过引入特殊的构建单元来制备的，这些构建单元能够形成酰胺、二硫键和配位键。脲桥常用于通过连接两个胺基官能化的侧链来制备环肽。在这里，我们提出了脲骨干环化作为制备骨干环肽文库的另一种方法。本文提出了一种用于合成结晶 Fmoc-N(alpha)[ω-氨基（Alloc）-烷基]甘氨酸构建单元的简便方法。我们合成了一组脲骨干环化的糖原合酶激酶 3 类似物，并评估了它们作为抗癌先导物对蛋白激酶 B 的抑制作用。
