A modelling study of a non-concerted hydrolytic cycloaddition reaction by the catalytic antibody H11 Original Research Article

H11 is the first antibody reported to have dual activity as a non-concerted, Diels–Alderase and hydrolytic catalyst. It was previously shown to catalyse the cycloaddition of acetoxybutadiene 1a to N-alkyl maleimides 2 to afford hydroxy-substituted bicyclic adducts 3 with a 30% ee of a major isomer. To better understand this mechanism and the partial stereospecificity, a homology model of H11 was constructed and used in docking studies to evaluate potential antibody–ligand complexes. The model suggested the hydrolytic nature of H11 was due to Glu 95H acting as a catalytic base, and evaluation of the shape complementarity of the proposed antibody–ligand complexes confirmed at a semi-quantitative level the observation that the major enantiomer is produced in a 30% ee.