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Amino acids with fluorescent tetrazine ethers as bioorthogonal handles for peptide modification
A set of 3-bromo-1,2,4,5-tetrazines with three distinct substitutions have been used as reagents for late-stage functionalization of small molecules through nucleophilic aromatic substitution. Spectroscopic studies of the products obtained proved that tetrazine ethers are intrinsically fluorescent....
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096626/ https://www.ncbi.nlm.nih.gov/pubmed/35702248 http://dx.doi.org/10.1039/d2ra02531k |
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author | Ros, Enric Bellido, Marina Matarin, Joan A. Gallen, Albert Martínez, Manuel Rodríguez, Laura Verdaguer, Xavier Ribas de Pouplana, Lluís Riera, Antoni |
author_facet | Ros, Enric Bellido, Marina Matarin, Joan A. Gallen, Albert Martínez, Manuel Rodríguez, Laura Verdaguer, Xavier Ribas de Pouplana, Lluís Riera, Antoni |
author_sort | Ros, Enric |
collection | PubMed |
description | A set of 3-bromo-1,2,4,5-tetrazines with three distinct substitutions have been used as reagents for late-stage functionalization of small molecules through nucleophilic aromatic substitution. Spectroscopic studies of the products obtained proved that tetrazine ethers are intrinsically fluorescent. This fluorescence is lost upon inverse Electron-Demand Diels–Alder (iEDDA) cycloaddition with strained alkenes. Tetrazine-phenol ethers are rather interesting because they can undergo rapid iEDDA reactions with a second order rate constant (k(2)) compatible with bioorthogonal ligations. As a showcase, l-tyrosine was derivatized with 3-bromo-6-methyl-1,2,4,5-tetrazine and coupled to the peptide drug octreotide. This peptide was detected in cellular flow cytometry, and its fluorescence turned off through a bioorthogonal iEDDA cycloaddition with a strained alkene, showing for the first time the detection and reactivity of intrinsically fluorescent tetrazines in a biologically relevant context. The synthesis and characterization of fluorescent tetrazine ethers with bioorthogonal applicability pave the way for the generation of useful compounds for both detection and bioconjugation in vivo. |
format | Online Article Text |
id | pubmed-9096626 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-90966262022-06-13 Amino acids with fluorescent tetrazine ethers as bioorthogonal handles for peptide modification Ros, Enric Bellido, Marina Matarin, Joan A. Gallen, Albert Martínez, Manuel Rodríguez, Laura Verdaguer, Xavier Ribas de Pouplana, Lluís Riera, Antoni RSC Adv Chemistry A set of 3-bromo-1,2,4,5-tetrazines with three distinct substitutions have been used as reagents for late-stage functionalization of small molecules through nucleophilic aromatic substitution. Spectroscopic studies of the products obtained proved that tetrazine ethers are intrinsically fluorescent. This fluorescence is lost upon inverse Electron-Demand Diels–Alder (iEDDA) cycloaddition with strained alkenes. Tetrazine-phenol ethers are rather interesting because they can undergo rapid iEDDA reactions with a second order rate constant (k(2)) compatible with bioorthogonal ligations. As a showcase, l-tyrosine was derivatized with 3-bromo-6-methyl-1,2,4,5-tetrazine and coupled to the peptide drug octreotide. This peptide was detected in cellular flow cytometry, and its fluorescence turned off through a bioorthogonal iEDDA cycloaddition with a strained alkene, showing for the first time the detection and reactivity of intrinsically fluorescent tetrazines in a biologically relevant context. The synthesis and characterization of fluorescent tetrazine ethers with bioorthogonal applicability pave the way for the generation of useful compounds for both detection and bioconjugation in vivo. The Royal Society of Chemistry 2022-05-12 /pmc/articles/PMC9096626/ /pubmed/35702248 http://dx.doi.org/10.1039/d2ra02531k Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Ros, Enric Bellido, Marina Matarin, Joan A. Gallen, Albert Martínez, Manuel Rodríguez, Laura Verdaguer, Xavier Ribas de Pouplana, Lluís Riera, Antoni Amino acids with fluorescent tetrazine ethers as bioorthogonal handles for peptide modification |
title | Amino acids with fluorescent tetrazine ethers as bioorthogonal handles for peptide modification |
title_full | Amino acids with fluorescent tetrazine ethers as bioorthogonal handles for peptide modification |
title_fullStr | Amino acids with fluorescent tetrazine ethers as bioorthogonal handles for peptide modification |
title_full_unstemmed | Amino acids with fluorescent tetrazine ethers as bioorthogonal handles for peptide modification |
title_short | Amino acids with fluorescent tetrazine ethers as bioorthogonal handles for peptide modification |
title_sort | amino acids with fluorescent tetrazine ethers as bioorthogonal handles for peptide modification |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096626/ https://www.ncbi.nlm.nih.gov/pubmed/35702248 http://dx.doi.org/10.1039/d2ra02531k |
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