Novel method for the synthesis of urea backbone cyclic peptides using new Alloc‐protected glycine building units |
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| Authors: | Mattan Hurevich Yftah Tal‐Gan Shoshana Klein Yaniv Barda Alexander Levitzki Chaim Gilon |
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| Affiliation: | 1. Institute of Chemistry, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel;2. Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel |
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| Abstract: | 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‐Nα [ω‐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. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. |
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| Keywords: | urea backbone cyclization solid phase peptide synthesis cyclic peptides AGBU |
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