title: A modelling study of a non-concerted hydrolytic cycloaddition reaction by the catalytic antibody H11.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Strathclyde, Glasgow G4 0NR, UK.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Clark
authors.forename: Blair F
authors.initials: BF
authors.lastname: Johnston
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Suckling
authors.forename: Simon P
authors.initials: SP
authors.lastname: Mackay
mesh_terms: D017151:Antibodies, Catalytic / Q000737:chemistry*; D001665:Binding Sites; D003500:Cyclization; D006868:Hydrolysis; D008958:Models, Molecular
chemical_list: D017151:Antibodies, Catalytic