Novel method for the synthesis of urea backbone cyclic peptides using new Alloc-protected glycine building units

Mattan Hurevich, Yftah Tal-Gan, Shoshana Klein, Yaniv Barda, Alexander Levitzki, Chaim Gilon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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.Herewe 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.

Original languageAmerican English
Pages (from-to)178-185
Number of pages8
JournalJournal of Peptide Science
Volume16
Issue number4
DOIs
StatePublished - Apr 2010

Keywords

  • AGBU
  • Cyclic peptides
  • Solid phase peptide synthesis
  • Urea backbone cyclization

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