Molecular recognition of sec-alcohol enantiomers by Candida antarctica lipase B

A model to explain the enantioselectivity of Candida antarctica lipase B towards sec-alcohols based on structure activity and molecular modelling is presented. The origin of the enantioselectivity was found to be due to different modes of binding for the enantiomers. The fast enantiomer places its medium substituent in a site of limited size, the stereoselectivity pocket, whereas the slow enantiomer has to position the large substituent in that same pocket. Our modal is in agreement with the 24 different substrates tested. Only substituents smaller than n-propyl can be accommodated by the stereoselectivity pocket. Moreover, important unfavourable electrostatic interactions are involved between this region and halogenated substituents. The former requirement entails a high enantiomeric ratio (E) for sec-alcohols with a medium group smaller than n-propyl and a large group larger than n-propyl. The latter requirement allows high E only for short chain vic-halogenated alcohols. (C) 1998 Elsevier Science B.V. All rights reserved.