Morpholine Anchored Fluorogenic Toolkit: Unveiled Disease Allied Protein Fibrillation in Lysosomal Compartment of Live‐Cell and Drosophila Models DOI Open Access

P. Kavyashree,

Harry Wilson,

Akshay Silswal

et al.

Small, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

The aberrant accumulation of cytotoxic protein aggregates is a hallmark various neurodegenerative and non-neurodegenerative ailments, necessitating the development sensitive selective tools for their detection. Herein, we report series morpholine-anchored fluorescent probes, denoted as SC-nmor (n = 2, 4, 6), designed facile visualization aggregates. These probes display notable changes in photophysical properties upon binding with aggregates, owing to high sensitivity fibrillar microenvironment. Specifically, SC-4mor probe demonstrates strong selectivity aggregated insulin proteins over native insulin, accompanied by significant enhancement fluorescence lifetime. Live-cell imaging reveals an exclusive localization at lysosomal compartment. This feature enables accumulated fibrils induced pepstatin A. Additionally, vivo assessments on genetically mutated dietary-modified Drosophila melanogaster, representing disease models, demonstrate staining enhanced emission from eye lobes Aβ-mutated HSD brain samples, suggesting that can exhibit adequate retention minimal biological toxicity. also shows its capability cross blood-brain barrier mice model. Consequently, emerges promising marker detecting monitoring neurotoxic fibrillation live cells animal offering potential insights into pathogenesis progression aggregation.

Language: Английский

Morpholine Anchored Fluorogenic Toolkit: Unveiled Disease Allied Protein Fibrillation in Lysosomal Compartment of Live‐Cell and Drosophila Models DOI Open Access

P. Kavyashree,

Harry Wilson,

Akshay Silswal

et al.

Small, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

The aberrant accumulation of cytotoxic protein aggregates is a hallmark various neurodegenerative and non-neurodegenerative ailments, necessitating the development sensitive selective tools for their detection. Herein, we report series morpholine-anchored fluorescent probes, denoted as SC-nmor (n = 2, 4, 6), designed facile visualization aggregates. These probes display notable changes in photophysical properties upon binding with aggregates, owing to high sensitivity fibrillar microenvironment. Specifically, SC-4mor probe demonstrates strong selectivity aggregated insulin proteins over native insulin, accompanied by significant enhancement fluorescence lifetime. Live-cell imaging reveals an exclusive localization at lysosomal compartment. This feature enables accumulated fibrils induced pepstatin A. Additionally, vivo assessments on genetically mutated dietary-modified Drosophila melanogaster, representing disease models, demonstrate staining enhanced emission from eye lobes Aβ-mutated HSD brain samples, suggesting that can exhibit adequate retention minimal biological toxicity. also shows its capability cross blood-brain barrier mice model. Consequently, emerges promising marker detecting monitoring neurotoxic fibrillation live cells animal offering potential insights into pathogenesis progression aggregation.

Language: Английский

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