title: A synthetic receptor for asymmetric dimethyl arginine.
abstract: Dynamic combinatorial chemistry was utilized to identify a novel small molecule receptor, A2D, for asymmetric dimethyl arginine (aRMe2), which is a post-translational modification (PTM) in proteins. It is known to play a role in a number of diseases, including spinal muscular atrophy, leukemia, lymphoma, and breast cancer. The receptor exhibits 2.5-7.5-fold selectivity over the isomeric symmetric dimethyl arginine, depending on the surrounding sequence, with binding affinities in the low micromolar range. The affinity and selectivity of A2D for the different methylated states of Arg parallels that of proteins that bind to these PTMs. Characterization of the receptor-PTM complex indicates that cation-π interactions provide the main driving force for binding, loosely mimicking the binding mode found in the recognition of dimethyl arginine by native protein receptors.
authors.affiliation: Department of Chemistry, CB 3290, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Lindsey I
authors.initials: LI
authors.lastname: James
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Beaver
authors.forename: Natalie W
authors.initials: NW
authors.lastname: Rice
authors.forename: Marcey L
authors.initials: ML
authors.lastname: Waters
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D008958:Models, Molecular; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011955:Receptors, Drug / Q000737:chemistry*; D054852:Small Molecule Libraries
chemical_list: D011955:Receptors, Drug; D054852:Small Molecule Libraries; C018524:N,N-dimethylarginine; D001120:Arginine