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NMR solution structure of a peptide from the mdm-2 binding domain of the p53 protein that is selectively cytotoxic to cancer cells.

Authors
Rosal-R; Pincus-MR; Brandt-Rauf-PW; Fine-RL; Michl-J; Wang-H
Source
Biochemistry 2004 Feb; 43(7):1854-1861
NIOSHTIC No.
20029376
Abstract
We have recently found that a peptide from the mdm-2 binding domain of the p53 protein induced rapid membranolytic necrosis of a variety of different human cancer cell lines. To determine the role of solution structure in this peptide's selective and rapid tumor membrane disruptive behavior, we have performed two-dimensional NMR on a 32-residue sequence called PNC-27, in both an aqueous cytosolic-like and a mixed organic membrane-mimetic solution environment. In an aqueous milieu, PNC-27 contains three alpha-helical domains connected by loop structures, forming an S shape, and another similar structure with less helical structure. In a solution environment simulating a membrane, the helical domains found in water increase in length, forming three classes of structures, all of which form a U-shaped helix-coil-helix ensemble. In both solvent systems, this peptide forms amphipathic structures such that its hydrophobic residues coalesce on one face while the polar residues aggregate on the opposite face. The ability to form these unique structures in these two solution environments may allow the PNC-27 peptide to selectively and rapidly disrupt cancer cell membranes.
Keywords
Peptides; Cell-damage; Cancer; Cytotoxicity; Cytotoxins; Cytotoxic-effects
Contact
Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, 60 Haven Avenue, New York, New York 10032
CODEN
BICHAW
Publication Date
20040224
Document Type
Journal Article
Funding Type
Grant
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-007590
Issue of Publication
7
ISSN
0006-2960
Priority Area
Research Tools and Approaches: Cancer Research Methods
Source Name
Biochemistry
State
NY
Performing Organization
Columbia University Health Sciences
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