Premium
Fmoc‐based chemical synthesis and selective binding to supercoiled DNA of the p53 C ‐terminal segment and its phosphorylated and acetylated derivatives
Author(s) -
Teruya Kenta,
Murphy Angela C.,
Burlin Tom,
Appella Ettore,
Mazur Sharlyn J.
Publication year - 2004
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.552
Subject(s) - acetylation , peptide , linker , chemistry , amino acid , phosphorylation , peptide synthesis , combinatorial chemistry , protecting group , stereochemistry , binding domain , dna , solid phase synthesis , n terminus , biochemistry , peptide sequence , binding site , organic chemistry , alkyl , computer science , gene , operating system
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. Published in 2004 by the European Peptide Society and John Wiley & Sons, Ltd.