The goal of this study is to improve the synthetic scope afforded by enzymatic catalysis in organic solvents, for asymmetric transformation leading to the synthesis of biomedical compounds. The mechanism of enzyme catalysis in non-aqueous media, and the effect or organic solvents on the enzyme structure is not well understood. As a result, the enzyme selectivity (pro-chiral selectivity and enantioslectivity) of any given reactions can not be predicted, and therefore, enzyme catalysis in organic solvents can not be used efficiently and successfully for the purposes mentioned above. The objectives of this study are: (a), to determine the mechanism of enzyme catalysis in organ solvents, by studying the effect of organic solvents on the structure of subtilisin C., and by studying the physicochemical properties of the solvents which affect the enzyme enantioselectivity; (b), to study the properties (enhanced enantioselectivity, stability, and catalytic rate)of subtilisin C.- cyclodextrin mixtures in organic solvents. This new enzyme preparation has been shown to exhibit higher reaction rates and enantioselectivity, and to preserve the enzyme secondary structure during lyophilization (preliminary results). Therefore, it has the potential to become the enzyme preparation of choice for the synthesis of biomedical relevant compounds. The ultimate goal of this project is to find a system in which the enzyme enantioslectivity of any given reaction can be rationally predicted in any solvent. Enzyme catalysis in organ solvents will become a powerful tool for the syntheses of chiral biologically active compounds.

Project Start
2000-04-01
Project End
2001-03-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
17
Fiscal Year
2000
Total Cost
$170,027
Indirect Cost
Name
University of Puerto Rico at Humacao
Department
Type
DUNS #
City
Humacao
State
PR
Country
United States
Zip Code
00791
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