Cargando…
Proteophenes – Amino Acid Functionalized Thiophene‐based Fluorescent Ligands for Visualization of Protein Deposits in Tissue Sections with Alzheimer's Disease Pathology
Protein deposits composed of specific proteins or peptides are associated with several neurodegenerative diseases and fluorescent ligands able to detect these pathological hallmarks are vital. Here, we report the synthesis of a class of thiophene‐based ligands, denoted proteophenes, with different a...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643645/ https://www.ncbi.nlm.nih.gov/pubmed/35950816 http://dx.doi.org/10.1002/chem.202201557 |
_version_ | 1784826566176407552 |
---|---|
author | Björk, Linnea Bäck, Marcus Lantz, Linda Ghetti, Bernardino Vidal, Ruben Klingstedt, Therése Nilsson, K. Peter R. |
author_facet | Björk, Linnea Bäck, Marcus Lantz, Linda Ghetti, Bernardino Vidal, Ruben Klingstedt, Therése Nilsson, K. Peter R. |
author_sort | Björk, Linnea |
collection | PubMed |
description | Protein deposits composed of specific proteins or peptides are associated with several neurodegenerative diseases and fluorescent ligands able to detect these pathological hallmarks are vital. Here, we report the synthesis of a class of thiophene‐based ligands, denoted proteophenes, with different amino acid side‐chain functionalities along the conjugated backbone, which display selectivity towards specific disease‐associated protein aggregates in tissue sections with Alzheimer's disease (AD) pathology. The selectivity of the ligands towards AD associated pathological hallmarks, such as aggregates of the amyloid‐β (Aβ) peptide or tau filamentous inclusions, was highly dependent on the chemical nature of the amino acid functionality, as well as on the location of the functionality along the pentameric thiophene backbone. Finally, the concept of synthesizing donor‐acceptor‐donor proteophenes with distinct photophysical properties was shown. Our findings provide the structural and functional basis for the development of new thiophene‐based ligands that can be utilized for optical assignment of different aggregated proteinaceous species in tissue sections. |
format | Online Article Text |
id | pubmed-9643645 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96436452023-01-09 Proteophenes – Amino Acid Functionalized Thiophene‐based Fluorescent Ligands for Visualization of Protein Deposits in Tissue Sections with Alzheimer's Disease Pathology Björk, Linnea Bäck, Marcus Lantz, Linda Ghetti, Bernardino Vidal, Ruben Klingstedt, Therése Nilsson, K. Peter R. Chemistry Research Articles Protein deposits composed of specific proteins or peptides are associated with several neurodegenerative diseases and fluorescent ligands able to detect these pathological hallmarks are vital. Here, we report the synthesis of a class of thiophene‐based ligands, denoted proteophenes, with different amino acid side‐chain functionalities along the conjugated backbone, which display selectivity towards specific disease‐associated protein aggregates in tissue sections with Alzheimer's disease (AD) pathology. The selectivity of the ligands towards AD associated pathological hallmarks, such as aggregates of the amyloid‐β (Aβ) peptide or tau filamentous inclusions, was highly dependent on the chemical nature of the amino acid functionality, as well as on the location of the functionality along the pentameric thiophene backbone. Finally, the concept of synthesizing donor‐acceptor‐donor proteophenes with distinct photophysical properties was shown. Our findings provide the structural and functional basis for the development of new thiophene‐based ligands that can be utilized for optical assignment of different aggregated proteinaceous species in tissue sections. John Wiley and Sons Inc. 2022-09-05 2022-11-07 /pmc/articles/PMC9643645/ /pubmed/35950816 http://dx.doi.org/10.1002/chem.202201557 Text en © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Articles Björk, Linnea Bäck, Marcus Lantz, Linda Ghetti, Bernardino Vidal, Ruben Klingstedt, Therése Nilsson, K. Peter R. Proteophenes – Amino Acid Functionalized Thiophene‐based Fluorescent Ligands for Visualization of Protein Deposits in Tissue Sections with Alzheimer's Disease Pathology |
title | Proteophenes – Amino Acid Functionalized Thiophene‐based Fluorescent Ligands for Visualization of Protein Deposits in Tissue Sections with Alzheimer's Disease Pathology |
title_full | Proteophenes – Amino Acid Functionalized Thiophene‐based Fluorescent Ligands for Visualization of Protein Deposits in Tissue Sections with Alzheimer's Disease Pathology |
title_fullStr | Proteophenes – Amino Acid Functionalized Thiophene‐based Fluorescent Ligands for Visualization of Protein Deposits in Tissue Sections with Alzheimer's Disease Pathology |
title_full_unstemmed | Proteophenes – Amino Acid Functionalized Thiophene‐based Fluorescent Ligands for Visualization of Protein Deposits in Tissue Sections with Alzheimer's Disease Pathology |
title_short | Proteophenes – Amino Acid Functionalized Thiophene‐based Fluorescent Ligands for Visualization of Protein Deposits in Tissue Sections with Alzheimer's Disease Pathology |
title_sort | proteophenes – amino acid functionalized thiophene‐based fluorescent ligands for visualization of protein deposits in tissue sections with alzheimer's disease pathology |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643645/ https://www.ncbi.nlm.nih.gov/pubmed/35950816 http://dx.doi.org/10.1002/chem.202201557 |
work_keys_str_mv | AT bjorklinnea proteophenesaminoacidfunctionalizedthiophenebasedfluorescentligandsforvisualizationofproteindepositsintissuesectionswithalzheimersdiseasepathology AT backmarcus proteophenesaminoacidfunctionalizedthiophenebasedfluorescentligandsforvisualizationofproteindepositsintissuesectionswithalzheimersdiseasepathology AT lantzlinda proteophenesaminoacidfunctionalizedthiophenebasedfluorescentligandsforvisualizationofproteindepositsintissuesectionswithalzheimersdiseasepathology AT ghettibernardino proteophenesaminoacidfunctionalizedthiophenebasedfluorescentligandsforvisualizationofproteindepositsintissuesectionswithalzheimersdiseasepathology AT vidalruben proteophenesaminoacidfunctionalizedthiophenebasedfluorescentligandsforvisualizationofproteindepositsintissuesectionswithalzheimersdiseasepathology AT klingstedttherese proteophenesaminoacidfunctionalizedthiophenebasedfluorescentligandsforvisualizationofproteindepositsintissuesectionswithalzheimersdiseasepathology AT nilssonkpeterr proteophenesaminoacidfunctionalizedthiophenebasedfluorescentligandsforvisualizationofproteindepositsintissuesectionswithalzheimersdiseasepathology |