Cargando…

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....

Descripción completa

Detalles Bibliográficos
Autores principales: Ros, Enric, Bellido, Marina, Matarin, Joan A., Gallen, Albert, Martínez, Manuel, Rodríguez, Laura, Verdaguer, Xavier, Ribas de Pouplana, Lluís, Riera, Antoni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2022
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
_version_ 1784706019354476544
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
work_keys_str_mv AT rosenric aminoacidswithfluorescenttetrazineethersasbioorthogonalhandlesforpeptidemodification
AT bellidomarina aminoacidswithfluorescenttetrazineethersasbioorthogonalhandlesforpeptidemodification
AT matarinjoana aminoacidswithfluorescenttetrazineethersasbioorthogonalhandlesforpeptidemodification
AT gallenalbert aminoacidswithfluorescenttetrazineethersasbioorthogonalhandlesforpeptidemodification
AT martinezmanuel aminoacidswithfluorescenttetrazineethersasbioorthogonalhandlesforpeptidemodification
AT rodriguezlaura aminoacidswithfluorescenttetrazineethersasbioorthogonalhandlesforpeptidemodification
AT verdaguerxavier aminoacidswithfluorescenttetrazineethersasbioorthogonalhandlesforpeptidemodification
AT ribasdepouplanalluis aminoacidswithfluorescenttetrazineethersasbioorthogonalhandlesforpeptidemodification
AT rieraantoni aminoacidswithfluorescenttetrazineethersasbioorthogonalhandlesforpeptidemodification