Candida antarctica Lipase A-Based Enantiorecognition of a Highly Strained 4-Dibenzocyclooctynol (DIBO) Used for PET Imaging

• Published in: Molecules
• Main Authors: Saija Sirén, Käthe M. Dahlström, Rakesh Puttreddy, Kari Rissanen, Tiina A. Salminen, Mika Scheinin, Xiang-Guo Li, Arto Liljeblad
• Format: Article in Journal/Newspaper
• Language: English
• Published: MDPI AG 2020
• Subjects: biocatalysis; lipase a from candida antarctica; dibo; kinetic resolution; molecular modeling; Organic chemistry; QD241-441; Antarc*; Antarctica
• Online Access: https://doi.org/10.3390/molecules25040879; https://doaj.org/article/0e87ff35b5b544f9b26f0ac22796bc79

The enantiomers of aromatic 4-dibenzocyclooctynol (DIBO), used for radiolabeling and subsequent conjugation of biomolecules to form radioligands for positron emission tomography (PET), were separated by kinetic resolution using lipase A from Candida antarctica (CAL-A). In optimized conditions, ( R )-DIBO [( R )- 1 , ee 95%] and its acetylated ( S )-ester [( S )- 2 , ee 96%] were isolated. In silico docking results explained the ability of CAL-A to differentiate the enantiomers of DIBO and to accommodate various acyl donors. Anhydrous MgCl 2 was used for binding water from the reaction medium and, thus, for obtaining higher conversion by preventing hydrolysis of the product ( S )- 2 into the starting material. Since the presence of hydrated MgCl 2 ·6H 2 O also allowed high conversion or effect on enantioselectivity, Mg 2+ ion was suspected to interact with the enzyme. Binding site predictions indicated at least two sites of interest; one in the lid domain at the bottom of the acyl binding pocket and another at the interface of the hydrolase and flap domains, just above the active site.