Influence of δ‐Functional Groups on the Enantiorecognition of Secondary Alcohols by Candida antarctica Lipase B
Abstract The selectivity of acetylation of δ‐functionalized secondary alcohols catalyzed by Candida antarctica lipase B has been examined by molecular dynamics. The results from the simulation show that a δ‐alcohol functionality forms a hydrogen bond with the carbonyl group of Thr 40. This interacti...
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crwiley:10.1002/cbic.200800036 2024-06-02T07:58:15+00:00 Influence of δ‐Functional Groups on the Enantiorecognition of Secondary Alcohols by Candida antarctica Lipase B Nyhlén, Jonas Martín‐Matute, Belén Sandström, Anders G. Bocola, Marco Bäckvall, Jan‐E. 2008 http://dx.doi.org/10.1002/cbic.200800036 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcbic.200800036 https://onlinelibrary.wiley.com/doi/full/10.1002/cbic.200800036 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor ChemBioChem volume 9, issue 12, page 1968-1974 ISSN 1439-4227 1439-7633 journal-article 2008 crwiley https://doi.org/10.1002/cbic.200800036 2024-05-03T11:45:01Z Abstract The selectivity of acetylation of δ‐functionalized secondary alcohols catalyzed by Candida antarctica lipase B has been examined by molecular dynamics. The results from the simulation show that a δ‐alcohol functionality forms a hydrogen bond with the carbonyl group of Thr 40. This interaction stabilizes the tetrahedral intermediate and thus leads to selective acetylation of the R enantiomer. A stabilizing interaction of the δ‐( R )‐acetoxy group with the peptide NH of alanine 282 was also observed. No stabilizing interaction could be found for the δ‐keto functionality, and it is proposed that this is the reason for the experimentally observed decrease in enantioselectivity. From these results, it was hypothesized that the enantioselectivity could be restored by mutating the alanine in position 281 for serine. The mutation was made experimentally, and the results show that the E value increased from 9 to 120. Article in Journal/Newspaper Antarc* Antarctica Wiley Online Library ChemBioChem 9 12 1968 1974 |
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Open Polar |
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Wiley Online Library |
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crwiley |
language |
English |
description |
Abstract The selectivity of acetylation of δ‐functionalized secondary alcohols catalyzed by Candida antarctica lipase B has been examined by molecular dynamics. The results from the simulation show that a δ‐alcohol functionality forms a hydrogen bond with the carbonyl group of Thr 40. This interaction stabilizes the tetrahedral intermediate and thus leads to selective acetylation of the R enantiomer. A stabilizing interaction of the δ‐( R )‐acetoxy group with the peptide NH of alanine 282 was also observed. No stabilizing interaction could be found for the δ‐keto functionality, and it is proposed that this is the reason for the experimentally observed decrease in enantioselectivity. From these results, it was hypothesized that the enantioselectivity could be restored by mutating the alanine in position 281 for serine. The mutation was made experimentally, and the results show that the E value increased from 9 to 120. |
format |
Article in Journal/Newspaper |
author |
Nyhlén, Jonas Martín‐Matute, Belén Sandström, Anders G. Bocola, Marco Bäckvall, Jan‐E. |
spellingShingle |
Nyhlén, Jonas Martín‐Matute, Belén Sandström, Anders G. Bocola, Marco Bäckvall, Jan‐E. Influence of δ‐Functional Groups on the Enantiorecognition of Secondary Alcohols by Candida antarctica Lipase B |
author_facet |
Nyhlén, Jonas Martín‐Matute, Belén Sandström, Anders G. Bocola, Marco Bäckvall, Jan‐E. |
author_sort |
Nyhlén, Jonas |
title |
Influence of δ‐Functional Groups on the Enantiorecognition of Secondary Alcohols by Candida antarctica Lipase B |
title_short |
Influence of δ‐Functional Groups on the Enantiorecognition of Secondary Alcohols by Candida antarctica Lipase B |
title_full |
Influence of δ‐Functional Groups on the Enantiorecognition of Secondary Alcohols by Candida antarctica Lipase B |
title_fullStr |
Influence of δ‐Functional Groups on the Enantiorecognition of Secondary Alcohols by Candida antarctica Lipase B |
title_full_unstemmed |
Influence of δ‐Functional Groups on the Enantiorecognition of Secondary Alcohols by Candida antarctica Lipase B |
title_sort |
influence of δ‐functional groups on the enantiorecognition of secondary alcohols by candida antarctica lipase b |
publisher |
Wiley |
publishDate |
2008 |
url |
http://dx.doi.org/10.1002/cbic.200800036 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcbic.200800036 https://onlinelibrary.wiley.com/doi/full/10.1002/cbic.200800036 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
ChemBioChem volume 9, issue 12, page 1968-1974 ISSN 1439-4227 1439-7633 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/cbic.200800036 |
container_title |
ChemBioChem |
container_volume |
9 |
container_issue |
12 |
container_start_page |
1968 |
op_container_end_page |
1974 |
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1800741536242073600 |