Candida antarctica Lipase A-Based Enantiorecognition of a Highly Strained 4-Dibenzocyclooctynol (DIBO) Used for PET Imaging
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)-D...
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ftmdpi:oai:mdpi.com:/1420-3049/25/4/879/ 2023-08-20T04:02:01+02:00 Candida antarctica 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 agris 2020-02-17 application/pdf https://doi.org/10.3390/molecules25040879 EN eng Multidisciplinary Digital Publishing Institute Organic Chemistry https://dx.doi.org/10.3390/molecules25040879 https://creativecommons.org/licenses/by/4.0/ Molecules; Volume 25; Issue 4; Pages: 879 biocatalysis lipase A from Candida antarctica DIBO kinetic resolution molecular modeling Text 2020 ftmdpi https://doi.org/10.3390/molecules25040879 2023-07-31T23:07:36Z 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. Text Antarc* Antarctica MDPI Open Access Publishing Molecules 25 4 879 |
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Open Polar |
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MDPI Open Access Publishing |
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ftmdpi |
language |
English |
topic |
biocatalysis lipase A from Candida antarctica DIBO kinetic resolution molecular modeling |
spellingShingle |
biocatalysis lipase A from Candida antarctica DIBO kinetic resolution molecular modeling Saija Sirén Käthe M. Dahlström Rakesh Puttreddy Kari Rissanen Tiina A. Salminen Mika Scheinin Xiang-Guo Li Arto Liljeblad Candida antarctica Lipase A-Based Enantiorecognition of a Highly Strained 4-Dibenzocyclooctynol (DIBO) Used for PET Imaging |
topic_facet |
biocatalysis lipase A from Candida antarctica DIBO kinetic resolution molecular modeling |
description |
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. |
format |
Text |
author |
Saija Sirén Käthe M. Dahlström Rakesh Puttreddy Kari Rissanen Tiina A. Salminen Mika Scheinin Xiang-Guo Li Arto Liljeblad |
author_facet |
Saija Sirén Käthe M. Dahlström Rakesh Puttreddy Kari Rissanen Tiina A. Salminen Mika Scheinin Xiang-Guo Li Arto Liljeblad |
author_sort |
Saija Sirén |
title |
Candida antarctica Lipase A-Based Enantiorecognition of a Highly Strained 4-Dibenzocyclooctynol (DIBO) Used for PET Imaging |
title_short |
Candida antarctica Lipase A-Based Enantiorecognition of a Highly Strained 4-Dibenzocyclooctynol (DIBO) Used for PET Imaging |
title_full |
Candida antarctica Lipase A-Based Enantiorecognition of a Highly Strained 4-Dibenzocyclooctynol (DIBO) Used for PET Imaging |
title_fullStr |
Candida antarctica Lipase A-Based Enantiorecognition of a Highly Strained 4-Dibenzocyclooctynol (DIBO) Used for PET Imaging |
title_full_unstemmed |
Candida antarctica Lipase A-Based Enantiorecognition of a Highly Strained 4-Dibenzocyclooctynol (DIBO) Used for PET Imaging |
title_sort |
candida antarctica lipase a-based enantiorecognition of a highly strained 4-dibenzocyclooctynol (dibo) used for pet imaging |
publisher |
Multidisciplinary Digital Publishing Institute |
publishDate |
2020 |
url |
https://doi.org/10.3390/molecules25040879 |
op_coverage |
agris |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
Molecules; Volume 25; Issue 4; Pages: 879 |
op_relation |
Organic Chemistry https://dx.doi.org/10.3390/molecules25040879 |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.3390/molecules25040879 |
container_title |
Molecules |
container_volume |
25 |
container_issue |
4 |
container_start_page |
879 |
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1774712400539287552 |