Synthesis and biological evaluation of a 5-6-5 imidazole-phenyl-thiazole based alpha-helix mimetic.

Journal article

The development of small molecules that disrupt protein-protein interactions is a key goal in addressing a number of disease states. The alpha-helix is commonly found at protein interaction interfaces and has been the focus of substantial small molecule mimetic efforts. One of the primary drawbacks of many small molecule alpha-helix mimetics is their hydrophobic core structures. To address this problem we have developed a novel scaffold based on a more water soluble 5-6-5 imidazole-phenyl-thiazole core. An inhibitor of this class has been shown to disrupt the Cdc42/Dbs protein-protein interaction at micromolar concentrations and may be useful in overcoming Cdc42-induced tumor resistance to anticancer therapies.

Authors: Cummings, C; Ross, N; Katt, W; Hamilton, A

• Publication status: Published
• Journal: Organic letters
• Volume: 11
• Issue: 1
• Pages: 25-28
• Publication date: 2009-01-01
• DOI: 10.1021/ol8022962
• EISSN: 1523-7052
• ISSN: 1523-7060
• Language: English
• Keywords: Thiazoles; Biomimetic Materials; Protein Binding; Imidazoles; Molecular Structure; Structure-Activity Relationship; cdc42 GTP-Binding Protein; Molecular Mimicry; Dose-Response Relationship, Drug; Crystallography, X-Ray; Models, Molecular; Protein Structure, Secondary