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Substituted 1,4‐Benzodiazepine‐2,5‐diones as α ‐Helix Mimetic Antagonists of the HDM2‐p53 Protein–Protein Interaction
Author(s) -
Cummings Maxwell D.,
Schubert Carsten,
Parks Daniel J.,
Calvo Raul R.,
LaFrance Louis V.,
Lattanze Jennifer,
Milkiewicz Karen L.,
Lu Tianbao
Publication year - 2006
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2006.00365.x
Subject(s) - chemistry , protein–protein interaction , small molecule , helix (gastropod) , stereochemistry , computational biology , biophysics , biochemistry , biology , ecology , snail
Small molecule antagonists of protein–protein interactions represent a particular challenge for pharmaceutical discovery. One approach to finding molecules that can disrupt these interactions is to seek mimics of common protein structure motifs. We present an analysis of how molecules based on the 1,4‐benzodiazepine‐2,5‐dione scaffold serve to mimic the side‐chains presented by the hydrophobic face of two turns of an α ‐helix derived from the tumor suppressor protein p53, and thus antagonize the HDM2‐p53 protein–protein binding interaction.