title: Enantioselective proteins: selection, binding studies and molecular modeling of antibodies with affinity towards hydrophobic BINOL derivatives.
abstract: In this paper, the initial steps towards the design of novel artificial metalloenzymes that exploit proteins as a second coordination sphere for traditional metal-ligand catalysis are described. Phage display was employed to select and study antibody fragments capable of recognizing hydrophobic BINOL derivatives designed to mimic BINAP, a widely used ligand in asymmetric metal-catalyzed reactions. The binding affinities of the selected antibodies towards a series of haptens were evaluated by using ELISA assays. A homology model of one of the most selective antibodies was constructed, and a computer-assisted ligand-docking study was carried out to elucidate the binding of the hapten. It was shown that, due to the hydrophobic nature of the haptens, a higher level of theoretical treatment was required to identify the correct binding modes. A small selection of the antibodies was found to discriminate between enantiomers and small structural modifications of the BINOL derivatives. The selectivities arise from hydrophobic interactions, and we propose that the identified set of antibodies provides a foundation for a novel route to artificial metalloenzymes.
authors.affiliation: Department of Chemistry and Interdisciplinary Nanoscience Center, University of Aarhus, Langelandsgade 140, 8000 Aarhus C, Denmark. bsr@chem.au.dk
authors.forename: Brian Schou
authors.initials: BS
authors.lastname: Rasmussen
authors.forename: Jan Mondrup
authors.initials: JM
authors.lastname: Pedersen
authors.forename: Jesper
authors.initials: J
authors.lastname: Sørensen
authors.forename: Janni
authors.initials: J
authors.lastname: Egebjerg
authors.forename: Birgit
authors.initials: B
authors.lastname: Schiøtt
authors.forename: Kim Kusk
authors.initials: KK
authors.lastname: Mortensen
authors.forename: Troels
authors.initials: T
authors.lastname: Skrydstrup
mesh_terms: D000906:Antibodies / Q000737:chemistry*; D001665:Binding Sites; D001667:Binding, Competitive; D004797:Enzyme-Linked Immunosorbent Assay; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D045726:Metalloproteases / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009284:Naphthols / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000906:Antibodies; C406944:BINOL, naphthol; D008024:Ligands; D009284:Naphthols; D045726:Metalloproteases