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 language | English |
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Pages (from-to) | 479-493 |
Number of pages | 15 |
Journal | Journal of Peptide Science |
Volume | 10 |
Issue number | 8 |
DOIs | |
Publication status | Published - 2004 Aug 1 |
Externally published | Yes |
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