1. Department of Chemistry, Yale University, P. O. Box 208107, New Haven, Connecticut 06520 (USA), Fax: (+1)?203‐432‐6144;2. Department of Chemistry, Penn State University at Abington, 1600 Woodland, Abington, PA 19001 (USA)
Abstract:
Targeting Bcl‐x L /Bak : A family of rationally designed α‐helix mimetics with improved solubility and synthetic feasibility based on a benzoylurea scaffold is presented. These benzoylurea derivatives favor a linear conformation stabilized by an intramolecular hydrogen bond, and are able to mimic the spatial projection of the i, i+4, and i+7 residues of an α‐helix. Binding affinities of the benzoylurea derivatives to Bcl‐xL have been assessed using fluorescence polarization competition assays and isothermal titration calorimetry.
