Fmoc-based chemical synthesis and selective binding to supercoiled DNA of the p53 C-terminal segment and its phosphorylated and acetylated derivatives

Kenta Teruya, Angela C. Murphy, Tom Burlin, Ettore Appella, Sharlyn J. Mazur

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

The C-terminal domain of p53 comprises a linker, the tetramerization domain and the regulatory domain, and contains at least seven sites of potential post-translational modification. An improved strategy was developed for the synthesis of large peptides that contain phosphorylated amino acids and p53(303-393), a 91 -amino acid peptide, and three post-translationally modified derivatives were synthesized through the sequential condensation of three partially protected segments. Peptide thiolesters were prepared using the sulfonamide-based 'safety-catch' resin approach and employing Fmoc-based solid-phase peptide synthesis. At the N-terminus of the middle building block, a photolabile protecting group, 3,4-dimethoxy-6-nitrobenzyloxycarbonyl, was incorporated to differentiate the N-terminal amino group from the side-chain amino groups. Two sequential couplings were accomplished following this protection strategy. The synthetic products, p53(303-393) and its phosphorylated or acetylated derivatives, exhibited the ability to bind specifically to supercoiled DNA, which is one of the characteristics of this domain.

Original languageEnglish
Pages (from-to)479-493
Number of pages15
JournalJournal of Peptide Science
Volume10
Issue number8
DOIs
Publication statusPublished - 2004 Aug 1
Externally publishedYes

Keywords

  • Peptide thiolester condensation
  • Photolabile protecting group
  • Safety-catch resin approach
  • Selective binding to supercoiled DNA
  • p53 C-terminal domain

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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