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The role of alpha-helical structure in p53 peptides as a determinant for their mechanism of cell death: necrosis versus apoptosis
Journal article   Peer reviewed

The role of alpha-helical structure in p53 peptides as a determinant for their mechanism of cell death: necrosis versus apoptosis

Ramon Rosal, Paul Brandt-Rauf, Matthew R. Pincus, Hsin Wang, Yuehua Mao, Yin Li and Robert L. Fine
Advanced drug delivery reviews, v 57(4), pp 653-660
2005
PMID: 15722169

Abstract

Alpha helical Apoptosis Necrosis NMR solution structure p53 Peptides
Peptides derived from the N-terminal and C-terminal regions of the p53 tumor suppressor protein, linked to the membrane transduction domain of Antennapedia, have both been found to have significant cytotoxic effects selectively in human cancer cells. However, the N-terminal and C-terminal p53 peptides apparently display very different mechanisms for their anticancer effects. These differential effects can be attributed to dissimilar abilities to form distinctive 3-dimensional structures in extracellular-matrix-like aqueous solution that enable unique and selective cancer cell membrane penetration and effect. N-terminally based p53 peptides, with their ability to form distinctive S-shaped helix–loop–helix structures, are able to rapidly disrupt cancer cell membranes via toroidal-like pore formation causing necrosis; conversely, C-terminally based p53 peptides, due to their more random coil configuration, can be transduced across cancer cell membranes and bind to its intracellular target to cause a Fas pathway mechanism of apoptosis.

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Collaboration types
Domestic collaboration
Web of Science research areas
Pharmacology & Pharmacy
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