Cupin Variants as a Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes
Nobutaka Fujieda, H. Ichihashi, Miho Yuasa, Yosuke Nishikawa, Genji Kurisu, Shinobu Itoh
Abstract
Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double-stranded β-barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo- and enantioselective Michael addition reaction of nitroalkanes to an α,β-unsaturated ketone. Moreover, calculated substrate docking signified C106N and F104W single-point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively.
Topics & Concepts
StereoselectivityMichael reactionChemistryStereochemistryLigand (biochemistry)MacromoleculeEnantioselective synthesisKetoneHistidineMutantDocking (animal)Combinatorial chemistryCatalysisOrganic chemistryBiochemistryEnzymeReceptorGeneMedicineNursingChemical Synthesis and AnalysisAsymmetric Hydrogenation and CatalysisSynthetic Organic Chemistry Methods