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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.

Authors
Rosal-R; Brandt-Rauf-P; Pincus-MR; Wang-H; Mao-Y; Li-Y; Fine-RL
Source
Adv Drug Deliv Rev 2005 Feb; 57(4):653-660
NIOSHTIC No.
20028921
Abstract
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.
Keywords
Peptides; Cell-damage; Cancer; Cytotoxicity; Cytotoxins; Cytotoxic-effects
Contact
Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, 701 West 168th Street rm. 5-531, New York, NY 10032, USA
CODEN
ADDREP
Publication Date
20050228
Document Type
Journal Article
Funding Type
Grant
Fiscal Year
2005
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-007590
Issue of Publication
4
ISSN
0169-409X
Priority Area
Research Tools and Approaches: Cancer Research Methods
Source Name
Advanced Drug Delivery Reviews
State
NY
Performing Organization
Columbia University Health Sciences
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