Posttranslational mutagenesis: A chemical strategy for exploring protein side-chain diversity
Post-translational modification of proteins expands their structural and functional capabilities beyond those directly specified by the genetic code. However, the vast diversity of chemically-plausible (including unnatural but functionally relevant) side-chains is not readily accessible. We describe...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
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American Association for the Advancement of Science
2016
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| _version_ | 1826285143504977920 |
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| author | Wright, T Bower, B Chalker, J Bernardes, G Wiewiora, R Ng, W Raj, R Faulkner, S Vallée, M Phanumartwiwath, A Coleman, O Thézénas, M Khan, M Galan, S Lercher, L Schombs, M Gerstberger, S Palm-Espling, M Baldwin, A Kessler, B Claridge, T Mohammed, S Davis, B |
| author_facet | Wright, T Bower, B Chalker, J Bernardes, G Wiewiora, R Ng, W Raj, R Faulkner, S Vallée, M Phanumartwiwath, A Coleman, O Thézénas, M Khan, M Galan, S Lercher, L Schombs, M Gerstberger, S Palm-Espling, M Baldwin, A Kessler, B Claridge, T Mohammed, S Davis, B |
| author_sort | Wright, T |
| collection | OXFORD |
| description | Post-translational modification of proteins expands their structural and functional capabilities beyond those directly specified by the genetic code. However, the vast diversity of chemically-plausible (including unnatural but functionally relevant) side-chains is not readily accessible. We describe C(sp3)–C(sp3) bond-forming reactions on proteins under biocompatible conditions, which exploit unusual carbon free radical chemistry, and use them to form C–C bonds with altered side chains. We demonstrate how these transformations enable a wide-diversity of natural, unnatural, post-translationally-modified (methylated, glycosylated, phosphorylated, hydroxylated) and labeled (fluorinated, isotopically-labeled) side-chains to be added to a common, readily-accessible dehydroalanine precursor in a range of representative protein types and scaffolds. This approach, outside of the rigid constraints of the ribosome and enzymatic processing, may be modified more generally for accessing diverse proteins. |
| first_indexed | 2024-03-07T01:24:26Z |
| format | Journal article |
| id | oxford-uuid:9179e0bf-4fb4-4c67-bb52-742087c4be4d |
| institution | University of Oxford |
| last_indexed | 2024-03-07T01:24:26Z |
| publishDate | 2016 |
| publisher | American Association for the Advancement of Science |
| record_format | dspace |
| spelling | oxford-uuid:9179e0bf-4fb4-4c67-bb52-742087c4be4d2022-03-26T23:19:08ZPosttranslational mutagenesis: A chemical strategy for exploring protein side-chain diversityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9179e0bf-4fb4-4c67-bb52-742087c4be4dSymplectic Elements at OxfordAmerican Association for the Advancement of Science2016Wright, TBower, BChalker, JBernardes, GWiewiora, RNg, WRaj, RFaulkner, SVallée, MPhanumartwiwath, AColeman, OThézénas, MKhan, MGalan, SLercher, LSchombs, MGerstberger, SPalm-Espling, MBaldwin, AKessler, BClaridge, TMohammed, SDavis, BPost-translational modification of proteins expands their structural and functional capabilities beyond those directly specified by the genetic code. However, the vast diversity of chemically-plausible (including unnatural but functionally relevant) side-chains is not readily accessible. We describe C(sp3)–C(sp3) bond-forming reactions on proteins under biocompatible conditions, which exploit unusual carbon free radical chemistry, and use them to form C–C bonds with altered side chains. We demonstrate how these transformations enable a wide-diversity of natural, unnatural, post-translationally-modified (methylated, glycosylated, phosphorylated, hydroxylated) and labeled (fluorinated, isotopically-labeled) side-chains to be added to a common, readily-accessible dehydroalanine precursor in a range of representative protein types and scaffolds. This approach, outside of the rigid constraints of the ribosome and enzymatic processing, may be modified more generally for accessing diverse proteins. |
| spellingShingle | Wright, T Bower, B Chalker, J Bernardes, G Wiewiora, R Ng, W Raj, R Faulkner, S Vallée, M Phanumartwiwath, A Coleman, O Thézénas, M Khan, M Galan, S Lercher, L Schombs, M Gerstberger, S Palm-Espling, M Baldwin, A Kessler, B Claridge, T Mohammed, S Davis, B Posttranslational mutagenesis: A chemical strategy for exploring protein side-chain diversity |
| title | Posttranslational mutagenesis: A chemical strategy for exploring protein side-chain diversity |
| title_full | Posttranslational mutagenesis: A chemical strategy for exploring protein side-chain diversity |
| title_fullStr | Posttranslational mutagenesis: A chemical strategy for exploring protein side-chain diversity |
| title_full_unstemmed | Posttranslational mutagenesis: A chemical strategy for exploring protein side-chain diversity |
| title_short | Posttranslational mutagenesis: A chemical strategy for exploring protein side-chain diversity |
| title_sort | posttranslational mutagenesis a chemical strategy for exploring protein side chain diversity |
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