Novel phosphoinositide-protein interactions and inhibition of Akt activation;
citation_date
2004-05
Description
The PI3K/Akt signaling pathway is critical for normal growth and development of a cell. The activation of Akt, while playing an important role in cell survival, has also been linked to cancer and diabetes. A specific Akt inhibitor is predicted to be of immense value in cancer treatment. Akt activation requires recruitment to the plasma membrane through interaction of its N-terminal pleckstrin homology (PH) domain with the phosphoinositide products of phosphatidylinositol-3-kinase (PI3K); phosphatidylinositol-3,4-bisphosphate (PI(3,4)P2) and (PI(3,4,5)P). Two synthe tic peptide libraries were screened for binding to the Akt PH domain using competitive displacement of PI(3,4)P2. One library consisted of random octamers and the second library was biased with alternate racemic glutamate or aspartate amino acids. Twenty-seven sequences were obtained and analyzed for Akt PH binding and the three sequences with highest affinity were chosen for further study. Each peptide demonstrated low micromolar in vitro
Type
text;
citation_publisher
University of Utah
citation_keywords
Signal Transduction; Peptides; Protein Kinases;
Subject (MESH)
Protease Inhibitors; Enzyme Inhibitors;
citation_dissertation_institution
University of Utah;
citation_dissertation_name
PhD;
citation_language
en;
Relation-Is Version Of
Digital reproduction of “Novel phosphoinositide-protein interactions and inhibition of Akt activation”. Spencer S. Eccles Health Sciences Library. Print version of “Novel phosphoinositide-protein interactions and inhibition of Akt activation” available at J. Willard Marriott Library Special Collection. QP6.5 2004 .B66.
