Sugar-mediated lyoprotection of purified human CYP3A4 and CYP2D6.
P450 enzymes are of great interest for drug metabolism and as potential biocatalysts. Like most P450s, purified CYP3A4 is normally handled and stored in solution because lyophilization greatly reduces its activity. We show here that colyophilization of this enzyme with sucrose or trehalose, but not mannitol, crown ethers or cyclodextrins, allow recovery of full enzymatic activity after rehydration. Sorbitol was almost as efficient, with 85% retention of the original activity. We also show that similar protection is observed through colyophilization of CYP2D6 with trehalose. This procedure should greatly facilitate handling, storage, or use of these enzymes in anhydrous media.
Chefson
Amandine
A
Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montréal, Québec, Canada.
Zhao
Jin
J
Auclair
Karine
K
D002241:Carbohydrates / Q000737:chemistry*; D002384:Catalysis; D019389:Cytochrome P-450 CYP2D6 / Q000737:chemistry*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D004789:Enzyme Activation; D006801:Humans
D002241:Carbohydrates; D003577:Cytochrome P-450 Enzyme System; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human