Proteophenes - Amino Acid Functionalized Thiophene-based Fluorescent Ligands for Visualization of Protein Deposits in Tissue Sections with Alzheimer's Disease Pathology

Overview

Journal Chemistry

Specialty Chemistry

Date 2022 Aug 11

PMID 35950816

Authors

Linnea Bjork

Marcus Back

Linda Lantz

Bernardino Ghetti

Ruben Vidal

Therese Klingstedt

K Peter R Nilsson

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Distinct Chemical Determinants are Essential for Achieving Ligands for Superior Optical Detection of Specific Amyloid-β Deposits in Alzheimer's Disease.

Wu X, Shirani H, Vidal R, Ghetti B, Ingelsson M, Klingstedt T ChemistryOpen. 2024; 13(12):e202400186.

PMID: 39508558 PMC: 11625938. DOI: 10.1002/open.202400186.

Distinct Heterocyclic Moieties Govern the Selectivity of Thiophene-Vinylene-Based Ligands Towards Aβ or Tau Pathology in Alzheime's Disease.

Bjork L, Shirani H, Todarwal Y, Linares M, Vidal R, Ghetti B European J Org Chem. 2024; 26(41).

PMID: 38585413 PMC: 10997339. DOI: 10.1002/ejoc.202300583.

Thiophene-Based Ligands: Design, Synthesis and Their Utilization for Optical Assignment of Polymorphic-Disease-Associated Protein Aggregates.

Bjork L, Klingstedt T, Nilsson K Chembiochem. 2023; 24(11):e202300044.

PMID: 36891883 PMC: 10404026. DOI: 10.1002/cbic.202300044.

Proteophenes - Amino Acid Functionalized Thiophene-based Fluorescent Ligands for Visualization of Protein Deposits in Tissue Sections with Alzheimer's Disease Pathology.

Bjork L, Back M, Lantz L, Ghetti B, Vidal R, Klingstedt T Chemistry. 2022; 28(62):e202201557.

PMID: 35950816 PMC: 9643645. DOI: 10.1002/chem.202201557.

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