Development of Highly Potent Inhibitors of the Ras‐Targeting Human Acyl Protein Thioesterases Based on Substrate Similarity Design
Christian Hedberg, Frank J. Dekker, Marion Rusch, Steffen Renner, Stefan Wetzel, Nachiket Vartak, Claas Gerding‐Reimers, Robin S. Bon, Philippe I. H. Bastiaens, Herbert Waldmann · Angewandte Chemie International Edition · 2011
A matter of common sense: a common recognition motif consisting of a negatively charged group five to six bonds away (red) from the (thio)ester functionality (green) and a positively charged tail group ten to twelve bonds away (blue) was identified in two native acyl protein thioesterase 1 (APT1) substrates. This similarity led to the design of potent inhibitors of the Ras-depalmitoylating enzyme APT1.