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ID: ALA1153909

Journal: Bioorg Med Chem

Title: Beta-peptides with improved affinity for hDM2 and hDMX.

Authors: Harker EA, Daniels DS, Guarracino DA, Schepartz A.

Abstract: We previously described a series of 3(14)-helical beta-peptides that bind the hDM2 protein and inhibit its interaction with a p53-derived peptide in vitro. Here we present a detailed characterization of the interaction of these peptides with hDM2 and report two new beta-peptides in which non-natural side chains have been substituted into the hDM2-recognition epitope. These peptides feature both improved affinity and inhibitory potency in fluorescence polarization and ELISA assays. Additionally, one of the new beta-peptides also binds the hDM2-related protein, hDMX, which has been identified as another key therapeutic target for activation of the p53 pathway in tumors.

CiteXplore: 19211253

DOI: 10.1016/j.bmc.2009.01.039