Solid-phase synthesis of chlorofusin analogues

Esther C. Y. Woon, Mariangela Arcieri, Andrew F. Wilderspin, John P. Malkinson, Mark Searcey

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

We report an efficient and versatile solid-phase synthesis through which two series of chlorofusin analogues, one bearing varying chromophores and the other with various amino acid substitutions in the cyclic peptide, were synthesized. These peptides were prepared using a strategy involving side-chain immobilization, on-resin cyclization, and postcyclization modification. The success of these syntheses demonstrates the broad utility of the method. Both series of analogues were evaluated for their inhibitory activity against the p53/MDM2 interaction but were shown to be inactive in the concentration range tested. This suggests that the full chromophore structure may be required for activity.
Original languageEnglish
Pages (from-to)5146-5151
Number of pages6
JournalJournal of Organic Chemistry
Volume72
Issue number14
DOIs
Publication statusPublished - 2007

Keywords

  • PEPTIDE
  • INHIBITOR
  • BINDING
  • PROTEIN
  • SMALL-MOLECULE ANTAGONISTS
  • MDM2
  • P53 PATHWAY
  • IN-VIVO
  • DISCOVERY

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