Picomolar-sensitive β-amyloid fibril fluorophores by tailoring the hydrophobicity of biannulated π-elongated dioxaborine-dyes

Jusung An; Peter Verwilst; Hira Aziz; Jinwoo Shin; Sungsu Lim; Ilwha Kim; Yun Kyung Kim; Jong Seung Kim

doi:10.1016/j.bioactmat.2021.10.047

Picomolar-sensitive β-amyloid fibril fluorophores by tailoring the hydrophobicity of biannulated π-elongated dioxaborine-dyes

Jusung An, Peter Verwilst, Hira Aziz, Jinwoo Shin, Sungsu Lim, Ilwha Kim, Yun Kyung Kim, Jong Seung Kim

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

Abstract

The pathological origin of Alzheimer's disease (AD) is still shrouded in mystery, despite intensive worldwide research efforts. The selective visualization of β-amyloid (Aβ), the most abundant proteinaceous deposit in AD, is pivotal to reveal AD pathology. To date, several small-molecule fluorophores for Aβ species have been developed, with increasing binding affinities. In the current work, two organic small-molecule dioxaborine-derived fluorophores were rationally designed through tailoring the hydrophobicity with the aim to enhance the binding affinity for Aβ_1-42 fibrils —while concurrently preventing poor aqueous solubility—via biannulate donor motifs in D-π-A dyes. An unprecedented sub-nanomolar affinity was found (K_d = 0.62 ± 0.33 nM) and applied to super-sensitive and red-emissive fluorescent staining of amyloid plaques in cortical brain tissue ex vivo. These fluorophores expand the dioxaborine-curcumin-based family of Aβ-sensitive fluorophores with a promising new imaging agent.

Original language	English
Pages (from-to)	239-248
Number of pages	10
Journal	Bioactive Materials
Volume	13
DOIs	https://doi.org/10.1016/j.bioactmat.2021.10.047
Publication status	Published - 2022 Jul

Bibliographical note

Funding Information:
This research was supported by the National Research Foundation of Korea (CRI project no. 2018R1A3B1052702, NRF-2019M3E5D1A01068998, J. S. Kim), the Korea University Graduate School Junior Fellow Research Grant (J. An), the National Research Council of Science & Technology (NST) granted by the Ministry of Science, ICT & Future Planning (MSIP) (No. CRC-15-04-KIST), the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) and Korea Dementia Research Center (KDRC), the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (No. HI20C1234), and P. V. acknowledges support from Interne Fondsen KU Leuven/Internal Funds KU Leuven (STG/19/029).

Funding Information:
This research was supported by the National Research Foundation of Korea (CRI project no. 2018R1A3B1052702 , NRF-2019M3E5D1A01068998 , J. S. Kim), the Korea University Graduate School Junior Fellow Research Grant (J. An), the National Research Council of Science & Technology (NST) granted by the Ministry of Science, ICT & Future Planning (MSIP) (No. CRC-15-04-KIST ), the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) and Korea Dementia Research Center (KDRC) , the Ministry of Health & Welfare and Ministry of Science and ICT , Republic of Korea (No. HI20C1234 ), and P. V. acknowledges support from Interne Fondsen KU Leuven/ Internal Funds KU Leuven ( STG/19/029 ).

Publisher Copyright:
© 2021 The Authors

Keywords

Alzheimer's disease
Dioxaborine-dye
Hydrophobicity tailoring
Small-molecular fluorescent probe
β-Amyloid

ASJC Scopus subject areas

Biotechnology
Biomaterials
Biomedical Engineering

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10.1016/j.bioactmat.2021.10.047

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title = "Picomolar-sensitive β-amyloid fibril fluorophores by tailoring the hydrophobicity of biannulated π-elongated dioxaborine-dyes",

abstract = "The pathological origin of Alzheimer's disease (AD) is still shrouded in mystery, despite intensive worldwide research efforts. The selective visualization of β-amyloid (Aβ), the most abundant proteinaceous deposit in AD, is pivotal to reveal AD pathology. To date, several small-molecule fluorophores for Aβ species have been developed, with increasing binding affinities. In the current work, two organic small-molecule dioxaborine-derived fluorophores were rationally designed through tailoring the hydrophobicity with the aim to enhance the binding affinity for Aβ1-42 fibrils —while concurrently preventing poor aqueous solubility—via biannulate donor motifs in D-π-A dyes. An unprecedented sub-nanomolar affinity was found (Kd = 0.62 ± 0.33 nM) and applied to super-sensitive and red-emissive fluorescent staining of amyloid plaques in cortical brain tissue ex vivo. These fluorophores expand the dioxaborine-curcumin-based family of Aβ-sensitive fluorophores with a promising new imaging agent.",

keywords = "Alzheimer's disease, Dioxaborine-dye, Hydrophobicity tailoring, Small-molecular fluorescent probe, β-Amyloid",

author = "Jusung An and Peter Verwilst and Hira Aziz and Jinwoo Shin and Sungsu Lim and Ilwha Kim and Kim, {Yun Kyung} and Kim, {Jong Seung}",

note = "Funding Information: This research was supported by the National Research Foundation of Korea (CRI project no. 2018R1A3B1052702, NRF-2019M3E5D1A01068998, J. S. Kim), the Korea University Graduate School Junior Fellow Research Grant (J. An), the National Research Council of Science & Technology (NST) granted by the Ministry of Science, ICT & Future Planning (MSIP) (No. CRC-15-04-KIST), the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) and Korea Dementia Research Center (KDRC), the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (No. HI20C1234), and P. V. acknowledges support from Interne Fondsen KU Leuven/Internal Funds KU Leuven (STG/19/029). Funding Information: This research was supported by the National Research Foundation of Korea (CRI project no. 2018R1A3B1052702 , NRF-2019M3E5D1A01068998 , J. S. Kim), the Korea University Graduate School Junior Fellow Research Grant (J. An), the National Research Council of Science & Technology (NST) granted by the Ministry of Science, ICT & Future Planning (MSIP) (No. CRC-15-04-KIST ), the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) and Korea Dementia Research Center (KDRC) , the Ministry of Health & Welfare and Ministry of Science and ICT , Republic of Korea (No. HI20C1234 ), and P. V. acknowledges support from Interne Fondsen KU Leuven/ Internal Funds KU Leuven ( STG/19/029 ). Publisher Copyright: {\textcopyright} 2021 The Authors",

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AU - Verwilst, Peter

AU - Aziz, Hira

AU - Shin, Jinwoo

AU - Lim, Sungsu

AU - Kim, Ilwha

AU - Kim, Yun Kyung

AU - Kim, Jong Seung

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PY - 2022/7

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N2 - The pathological origin of Alzheimer's disease (AD) is still shrouded in mystery, despite intensive worldwide research efforts. The selective visualization of β-amyloid (Aβ), the most abundant proteinaceous deposit in AD, is pivotal to reveal AD pathology. To date, several small-molecule fluorophores for Aβ species have been developed, with increasing binding affinities. In the current work, two organic small-molecule dioxaborine-derived fluorophores were rationally designed through tailoring the hydrophobicity with the aim to enhance the binding affinity for Aβ1-42 fibrils —while concurrently preventing poor aqueous solubility—via biannulate donor motifs in D-π-A dyes. An unprecedented sub-nanomolar affinity was found (Kd = 0.62 ± 0.33 nM) and applied to super-sensitive and red-emissive fluorescent staining of amyloid plaques in cortical brain tissue ex vivo. These fluorophores expand the dioxaborine-curcumin-based family of Aβ-sensitive fluorophores with a promising new imaging agent.

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Picomolar-sensitive β-amyloid fibril fluorophores by tailoring the hydrophobicity of biannulated π-elongated dioxaborine-dyes

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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