Journal article
Peptides from the amino terminal mdm-2-binding domain of p53, designed from conformational analysis, are selectively cytotoxic to transformed cells
Proceedings of the National Academy of Sciences - PNAS, v 98(22), pp 12438-12443
16 Oct 2001
PMID: 11606716
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We have synthesized three peptides from the mdm-2 binding domain of human p53, residues 12–26 (PPLSQETFSDLWKLL), residues 12–20, and 17–26. To enable transport of the peptides across the cell membrane and at the same time to maximize the active mdm-2 binding α-helical conformation for these peptides, each was attached at its carboxyl terminus to the penetratin sequence, KKWKMRRNQFWVKVQRG, that contains many positively charged residues that stabilize an α-helix when present on its carboxyl terminal end. All three peptides were cytotoxic to human cancer cells in culture, whereas a control, unrelated peptide attached to the same penetratin sequence had no effect on these cell lines. The same three cytotoxic peptides had no effect on the growth of normal cells, including human cord blood-derived stem cells. These peptides were as effective in causing cell death in p53-null cancer cells as in those having mutant or normal p53. Peptide-induced cell death is not accompanied by expression of apoptosis-associated proteins such as Bax and
waf
p21
. Based on these findings, we conclude that the antiproliferative effects of these p53-derived peptides are not completely dependent on p53 activity and may prove useful as general anticancer agents.
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Details
- Title
- Peptides from the amino terminal mdm-2-binding domain of p53, designed from conformational analysis, are selectively cytotoxic to transformed cells
- Creators
- Mecheal Kanovsky - Veterans Health AdministrationAnthony RaffoLisa DrewRamon RosalTamara DoFred K. FriedmanPablo RubinsteinJan VisserRichard RobinsonPaul W. Brandt-RaufJosef MichlRobert L. FineMatthew R. Pincus
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 98(22), pp 12438-12443
- Publisher
- The National Academy of Sciences
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Web of Science ID
- WOS:000171806100029
- Scopus ID
- 2-s2.0-0035940401
- Other Identifier
- 991019323783804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology