<i>Candida antarctica</i> Lipase A-Based Enantiorecognition of a Highly Strained 4-Dibenzocyclooctynol (DIBO) Used for PET Imaging
Saija Sirén,
Käthe M. Dahlström,
Rakesh Puttreddy,
Kari Rissanen,
Tiina A. Salminen,
Mika Scheinin,
Xiang-Guo Li,
Arto Liljeblad
Affiliations
Saija Sirén
Laboratory of Synthetic Drug Chemistry, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FI-20520 Turku, Finland
Käthe M. Dahlström
Structural Bioinformatics Laboratory, Biochemistry, Faculty of Science and Engineering, Åbo Akademi University, Tykistökatu 6 A, FI-20520 Turku, Finland
Rakesh Puttreddy
Department of Chemistry, University of Jyväskylä, P.O. Box 35, FI-40014 Jyväskylä, Finland
Kari Rissanen
Department of Chemistry, University of Jyväskylä, P.O. Box 35, FI-40014 Jyväskylä, Finland
Tiina A. Salminen
Structural Bioinformatics Laboratory, Biochemistry, Faculty of Science and Engineering, Åbo Akademi University, Tykistökatu 6 A, FI-20520 Turku, Finland
Mika Scheinin
Institute of Biomedicine, University of Turku, and Unit of Clinical Pharmacology, Turku University Hospital, FI-20521 Turku, Finland
Xiang-Guo Li
Turku PET Centre, Åbo Akademi University and University of Turku, Kiinamyllynkatu 4-8, FI-20521 Turku, Finland
Arto Liljeblad
Laboratory of Synthetic Drug Chemistry, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FI-20520 Turku, Finland
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 MgCl2 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 MgCl2·6H2O also allowed high conversion or effect on enantioselectivity, Mg2+ 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.
