title: A combined computational and experimental approach for the analysis of the enantioselective potential of a new macrocyclic receptor for N-protected alpha-amino acids.
abstract: A new macrocyclic receptor incorporating a thiourea moiety has been synthesised. Crystal structures of the macrocycle showed that the receptor has a rigid backbone but the thiourea moiety can orientate itself to bind to a DMSO solvent molecule. Force-field (MMFFs) calculations were performed to model the macrocycle and its binding properties with respect to N-protected amino acids, which were measured experimentally by NMR titration. Binding free energies were calculated by using the mode integration algorithm (MINTA) or free-energy perturbation (FEP). Excellent qualitative agreement with experiment was obtained. To further exploit the accuracy of the free-energy predictions for this system, the faster free-energy algorithm MINTA was used as a prediction tool to test the binding affinity of the macrocycle towards a series of several other amino acid derivatives, which speeded up considerably the screening process and reduced laboratory costs.
authors.affiliation: School of Chemistry, University of Southampton, Southampton, SO17 1BJ, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ragusa
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Hayes
authors.forename: Mark E
authors.initials: ME
authors.lastname: Light
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Kilburn