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

• Main Authors: Sirén Saija, Salminen Tiina A., Puttreddy Rakesh, Liljeblad Arto, Rissanen Kari, Scheinin Mika, Li Xiang-Guo, Dahlström Käthe M.
• Other Authors: PET perustoiminta, PET Basic Operations, tyks, vsshp, tyks, vsshp, biolääketieteen laitos, yhteiset, Institute of Biomedicine, 2607100, 2609810
• Language: English
• Published: MDPI AG 2022
• Subjects: Antarc*; Antarctica
• Online Access: https://www.utupub.fi/handle/10024/157374

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.