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Opportunities for Expanding Encoded Chemical Diversification and Improving Hit Enrichment in mRNA‐Displayed Peptide Libraries
DNA‐encoded small‐molecule libraries and mRNA displayed peptide libraries both use numerically large pools of oligonucleotide‐tagged molecules to identify potential hits for protein targets. They differ dramatically, however, in the ‘drug‐likeness’ of the molecules that each can be used to discover....
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306583/ https://www.ncbi.nlm.nih.gov/pubmed/35100479 http://dx.doi.org/10.1002/cbic.202100685 |
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author | Melsen, Paddy R. A. Yoshisada, Ryoji Jongkees, Seino A. K. |
author_facet | Melsen, Paddy R. A. Yoshisada, Ryoji Jongkees, Seino A. K. |
author_sort | Melsen, Paddy R. A. |
collection | PubMed |
description | DNA‐encoded small‐molecule libraries and mRNA displayed peptide libraries both use numerically large pools of oligonucleotide‐tagged molecules to identify potential hits for protein targets. They differ dramatically, however, in the ‘drug‐likeness’ of the molecules that each can be used to discover. We give here an overview of the two techniques, comparing some advantages and disadvantages of each, and suggest areas where particularly mRNA display can benefit from adopting advances developed with DNA‐encoded small molecule libraries. We outline cases where chemical modification of the peptide library has already been used in mRNA display, and survey opportunities to expand this using examples from DNA‐encoded small molecule libraries. We also propose potential opportunities for encoding such reactions within the mRNA/cDNA tag of an mRNA‐displayed peptide library to allow a more diversity‐oriented approach to library modification. Finally, we outline alternate approaches for enriching target‐binding hits from a pooled and tagged library, and close by detailing several examples of how an adjusted mRNA‐display based approach could be used to discover new ‘drug‐like’ modified small peptides. |
format | Online Article Text |
id | pubmed-9306583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93065832022-07-28 Opportunities for Expanding Encoded Chemical Diversification and Improving Hit Enrichment in mRNA‐Displayed Peptide Libraries Melsen, Paddy R. A. Yoshisada, Ryoji Jongkees, Seino A. K. Chembiochem Reviews DNA‐encoded small‐molecule libraries and mRNA displayed peptide libraries both use numerically large pools of oligonucleotide‐tagged molecules to identify potential hits for protein targets. They differ dramatically, however, in the ‘drug‐likeness’ of the molecules that each can be used to discover. We give here an overview of the two techniques, comparing some advantages and disadvantages of each, and suggest areas where particularly mRNA display can benefit from adopting advances developed with DNA‐encoded small molecule libraries. We outline cases where chemical modification of the peptide library has already been used in mRNA display, and survey opportunities to expand this using examples from DNA‐encoded small molecule libraries. We also propose potential opportunities for encoding such reactions within the mRNA/cDNA tag of an mRNA‐displayed peptide library to allow a more diversity‐oriented approach to library modification. Finally, we outline alternate approaches for enriching target‐binding hits from a pooled and tagged library, and close by detailing several examples of how an adjusted mRNA‐display based approach could be used to discover new ‘drug‐like’ modified small peptides. John Wiley and Sons Inc. 2022-02-18 2022-06-20 /pmc/articles/PMC9306583/ /pubmed/35100479 http://dx.doi.org/10.1002/cbic.202100685 Text en © 2022 The Authors. ChemBioChem published by Wiley-VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Reviews Melsen, Paddy R. A. Yoshisada, Ryoji Jongkees, Seino A. K. Opportunities for Expanding Encoded Chemical Diversification and Improving Hit Enrichment in mRNA‐Displayed Peptide Libraries |
title | Opportunities for Expanding Encoded Chemical Diversification and Improving Hit Enrichment in mRNA‐Displayed Peptide Libraries |
title_full | Opportunities for Expanding Encoded Chemical Diversification and Improving Hit Enrichment in mRNA‐Displayed Peptide Libraries |
title_fullStr | Opportunities for Expanding Encoded Chemical Diversification and Improving Hit Enrichment in mRNA‐Displayed Peptide Libraries |
title_full_unstemmed | Opportunities for Expanding Encoded Chemical Diversification and Improving Hit Enrichment in mRNA‐Displayed Peptide Libraries |
title_short | Opportunities for Expanding Encoded Chemical Diversification and Improving Hit Enrichment in mRNA‐Displayed Peptide Libraries |
title_sort | opportunities for expanding encoded chemical diversification and improving hit enrichment in mrna‐displayed peptide libraries |
topic | Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306583/ https://www.ncbi.nlm.nih.gov/pubmed/35100479 http://dx.doi.org/10.1002/cbic.202100685 |
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