The aim of this project is to explore novel synthetic opportunities afforded by enzymatic catalysis in organic solvents, particularly for the development of asymmetric (and otherwise selective) transformations, and for their utilization in the production of biomedically relevant compounds. One of the draw-backs of using enzymes successfully and efficiently for the purpose mentioned above is the difficulty to predict the outcome of a given reaction, in a given organic solvent. To achieve this aim the effect of organic solvents on the enzyme's tertiary structure will be first ascertained. This will be accomplished by """"""""mapping"""""""" the enzyme's tertiary structure around the active site, in different organic solvents. Second, the study of solvent dependence of enzyme enantioselectivity will be extended to immobilized, cross-linked, and polymer-encapsulated enzyme preparations. The ultimate goal is to find a system in which the enantioselectivity of an enzyme can be rationally predicted in any organic solvent with any given substrate. Enzyme catalysis in organic solvents will became a powerful tool for the syntheses of chiral biologically active compounds.
|Montanez-Clemente, Ileana; Alvira, Edgardo; Macias, Minedys et al. (2002) Enzyme activation in organic solvents: co-lyophilization of subtilisin Carlsberg with methyl-beta-cyclodextrin renders an enzyme catalyst more active than the cross-linked enzyme crystals. Biotechnol Bioeng 78:53-9|
|Griebenow, K; Vidal, M; Baez, C et al. (2001) Nativelike enzyme properties are important for optimum activity in neat organic solvents. J Am Chem Soc 123:5380-1|