A1 Journal article (refereed)
Candida antarctica Lipase A-Based Enantiorecognition of a Highly Strained 4-Dibenzocyclooctynol (DIBO) Used for PET Imaging (2020)

Sirén, S., Dahlström, K. M., Puttreddy, R., Rissanen, K., Salminen, T. A., Scheinin, M., Li, X.-G., & Liljeblad, A. (2020). Candida antarctica Lipase A-Based Enantiorecognition of a Highly Strained 4-Dibenzocyclooctynol (DIBO) Used for PET Imaging. Molecules, 25(4), Article 879. https://doi.org/10.3390/molecules25040879

JYU authors or editors

Publication details

All authors or editors: Sirén, Saija; Dahlström, Käthe M.; Puttreddy, Rakesh; Rissanen, Kari; Salminen, Tiina A.; Scheinin, Mika; Li, Xiang-Guo; Liljeblad, Arto

Journal or series: Molecules

eISSN: 1420-3049

Publication year: 2020

Volume: 25

Issue number: 4

Article number: 879

Publisher: MDPI

Publication country: Switzerland

Publication language: English

DOI: https://doi.org/10.3390/molecules25040879

Publication open access: Openly available

Publication channel open access: Open Access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/68001

Abstract

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 MgCl26H2O 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.

Keywords: tracers (indicators); aromatic compounds; biocatalysis; naturally occurring substances; yeast fungi; enzymes; lipases; computational chemistry

Free keywords: biocatalysis; lipase A from Candida antarctica; DIBO; kinetic resolution; molecular modeling

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Ministry reporting: Yes

VIRTA submission year: 2020

JUFO rating: 1