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 mode lling is presented. The origin of the enantioselectivity was found to be due to different modes of binding for the enantiomers. The fast ena ntiomer places its medium substituent in a site of limited size, the s tereoselectivity pocket, whereas the slow enantiomer has to position t he large substituent in that same pocket. Our modal is in agreement wi th 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 betwe en this region and halogenated substituents. The former requirement en tails a high enantiomeric ratio (E) for sec-alcohols with a medium gro up smaller than n-propyl and a large group larger than n-propyl. The l atter requirement allows high E only for short chain vic-halogenated a lcohols. (C) 1998 Elsevier Science B.V. All rights reserved.