Novel phosphoinositide-protein interactions and inhibition of Akt activation

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Title Novel phosphoinositide-protein interactions and inhibition of Akt activation
Publication Type dissertation
School or College College of Pharmacy
Department Medicinal Chemistry
Author Booth, Randy Alan
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 <italic>in vitro
Type Text
Publisher University of Utah
Subject Signal Transduction; Peptides; Protein Kinases
Subject MESH Protease Inhibitors; Enzyme Inhibitors
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
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.
Rights Management © Randy Alan Booth.
Format application/pdf
Format Medium application/pdf
Format Extent 3,513,105 bytes
Identifier undthes,4090
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available)
Master File Extent 3,513,144 bytes
ARK ark:/87278/s6h70hpr
Setname ir_etd
ID 191377
Reference URL https://collections.lib.utah.edu/ark:/87278/s6h70hpr
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