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

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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.
Original languageEnglish
Pages (from-to)2674-2683
Number of pages9
JournalBioorganic and Medicinal Chemistry Letters
Volume14
DOIs
Publication statusPublished - 15 Apr 2006

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Keywords

  • modelling
  • cycloaddition
  • hydrolysis
  • antibody
  • Diels-Alderase

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