Identification of novel polyphenol oxidase inhibitors by enzymatic one‐pot synthesis and deconvolution of combinatorial libraries
Abstract The feasibility of enzymatic synthesis of combinatorial libraries using multifunctional starting materials [i.e., 2,4‐dihydroxy‐ N ‐(2‐hydroxyethyl)benzamide, 1; 4‐hydroxyphenethyl alcohol, 2; 3,5‐dihydroxybenzyl alcohol, 3; and 4‐hydroxybenzyl alcohol, 4 ] with six vinyl esters, in a one‐p...
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crwiley:10.1002/bit.1168 2024-06-02T07:56:22+00:00 Identification of novel polyphenol oxidase inhibitors by enzymatic one‐pot synthesis and deconvolution of combinatorial libraries de la Gôutte, Jérome Tricand Khan, Jeffrey A. Vulfson, Evgeny N. BBSRC 2001 http://dx.doi.org/10.1002/bit.1168 http://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fbit.1168 https://onlinelibrary.wiley.com/doi/pdf/10.1002/bit.1168 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor Biotechnology and Bioengineering volume 75, issue 1, page 93-99 ISSN 0006-3592 1097-0290 journal-article 2001 crwiley https://doi.org/10.1002/bit.1168 2024-05-03T11:45:14Z Abstract The feasibility of enzymatic synthesis of combinatorial libraries using multifunctional starting materials [i.e., 2,4‐dihydroxy‐ N ‐(2‐hydroxyethyl)benzamide, 1; 4‐hydroxyphenethyl alcohol, 2; 3,5‐dihydroxybenzyl alcohol, 3; and 4‐hydroxybenzyl alcohol, 4 ] with six vinyl esters, in a one‐pot reaction, was investigated. Candida antarctica lipase was employed as a biocatalyst. The resulting 24‐compound library contained all the expected species with no significant bias toward particular combinations of substrates. As expected, the library contained a substance(s) that showed significant inhibition of polyphenol oxidase, which was used as a model target. The deconvolution was accomplished via resynthesis of ten partial libraries, which were prepared with either an equimolar mixture of the four alcohols and a single vinyl ester, or a single alcohol and equimolar mixture of the activated esters. Analysis of the inhibition pattern observed with these partial libraries suggested that 4‐hydroxybenzyl benzoate (4e) should be the most potent inhibitor. This conclusion was confirmed by the preparation and comparison of all 24 components of the initial library. Finally, it was shown that 4e was a competitive inhibitor of polyphenol oxidase, with a K i of 40 μ M. This value compared favorably with a K i of 400 μ M, which was determined for parent phenol 4. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 75: 93–99, 2001. Article in Journal/Newspaper Antarc* Antarctica Wiley Online Library Biotechnology and Bioengineering 75 1 93 99 |
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Abstract The feasibility of enzymatic synthesis of combinatorial libraries using multifunctional starting materials [i.e., 2,4‐dihydroxy‐ N ‐(2‐hydroxyethyl)benzamide, 1; 4‐hydroxyphenethyl alcohol, 2; 3,5‐dihydroxybenzyl alcohol, 3; and 4‐hydroxybenzyl alcohol, 4 ] with six vinyl esters, in a one‐pot reaction, was investigated. Candida antarctica lipase was employed as a biocatalyst. The resulting 24‐compound library contained all the expected species with no significant bias toward particular combinations of substrates. As expected, the library contained a substance(s) that showed significant inhibition of polyphenol oxidase, which was used as a model target. The deconvolution was accomplished via resynthesis of ten partial libraries, which were prepared with either an equimolar mixture of the four alcohols and a single vinyl ester, or a single alcohol and equimolar mixture of the activated esters. Analysis of the inhibition pattern observed with these partial libraries suggested that 4‐hydroxybenzyl benzoate (4e) should be the most potent inhibitor. This conclusion was confirmed by the preparation and comparison of all 24 components of the initial library. Finally, it was shown that 4e was a competitive inhibitor of polyphenol oxidase, with a K i of 40 μ M. This value compared favorably with a K i of 400 μ M, which was determined for parent phenol 4. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 75: 93–99, 2001. |
author2 |
BBSRC |
format |
Article in Journal/Newspaper |
author |
de la Gôutte, Jérome Tricand Khan, Jeffrey A. Vulfson, Evgeny N. |
spellingShingle |
de la Gôutte, Jérome Tricand Khan, Jeffrey A. Vulfson, Evgeny N. Identification of novel polyphenol oxidase inhibitors by enzymatic one‐pot synthesis and deconvolution of combinatorial libraries |
author_facet |
de la Gôutte, Jérome Tricand Khan, Jeffrey A. Vulfson, Evgeny N. |
author_sort |
de la Gôutte, Jérome Tricand |
title |
Identification of novel polyphenol oxidase inhibitors by enzymatic one‐pot synthesis and deconvolution of combinatorial libraries |
title_short |
Identification of novel polyphenol oxidase inhibitors by enzymatic one‐pot synthesis and deconvolution of combinatorial libraries |
title_full |
Identification of novel polyphenol oxidase inhibitors by enzymatic one‐pot synthesis and deconvolution of combinatorial libraries |
title_fullStr |
Identification of novel polyphenol oxidase inhibitors by enzymatic one‐pot synthesis and deconvolution of combinatorial libraries |
title_full_unstemmed |
Identification of novel polyphenol oxidase inhibitors by enzymatic one‐pot synthesis and deconvolution of combinatorial libraries |
title_sort |
identification of novel polyphenol oxidase inhibitors by enzymatic one‐pot synthesis and deconvolution of combinatorial libraries |
publisher |
Wiley |
publishDate |
2001 |
url |
http://dx.doi.org/10.1002/bit.1168 http://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fbit.1168 https://onlinelibrary.wiley.com/doi/pdf/10.1002/bit.1168 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
Biotechnology and Bioengineering volume 75, issue 1, page 93-99 ISSN 0006-3592 1097-0290 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/bit.1168 |
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Biotechnology and Bioengineering |
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75 |
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1 |
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93 |
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99 |
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1800755471894708224 |