Sunday, April 29, 2007

Highly activite and soluble enzymes for derivatization of lead molecules in organic media

Abhijeet P. Borole and Brian H. Davison. Biosciences Division, Oak Ridge National Laboratory, 1-Bethel Valley Road, Bldg 1520, Rm 217, Oak Ridge, TN 37831

Activation of enzymes has been reported in organic media via lyophilization with salts. Using salt-activated enzymes to transform molecules tethered to solid surfaces in organic phase requires solubilization of enzymes in the solvents. The current poster reports on improving performance of enzymes via chemical modification, use of surfactants and a new method of enzyme-salt-surfactant complex preparation. This is demonstrated using esterase enzymes with transesterification of N-acetyl phenylalanine ethyl ester as the model reaction. Production of amino acid esters by subtilisin Carlsberg (SC) and other proteases/lipases were studied. A method to prepare highly dispersed enzymes in a salt-surfactant milieu was investigated. This was compared to enzymes activated using surfactants added after lyophilization. An enzyme preparation with 2-4 fold increased activity was demonstrated. The effect of different surfactants and relationship with reaction solvents was studied. The potential of these preparations for solid-phase synthesis and drug molecule derivatization will be presented.