Supporting data from: Catalytic photooxygenation demonstrates therapeutic efficacy in transthyretin amyloidosis
Data files
Mar 04, 2026 version files 16.22 GB
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DatasetS1toS14_CSV.7z
26.29 KB
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DatasetS1toS14.7z
16.10 MB
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MovieS1.7z
6.99 GB
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MovieS2.7z
4.40 GB
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MovieS3.7z
4.81 GB
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README.md
6.40 KB
Abstract
The escalating global trend of aging populations has brought attention to the rising prevalence of late-onset amyloid disorders. Among them, amyloid transthyretin (ATTR) amyloidosis presents a growing area of unmet medical needs. While current treatment modalities have demonstrated efficacy in preventing or delaying amyloid generation, methodology to selectively modify and neutralize existing amyloid burdens remains inadequately addressed, leaving the fundamental irreversibility and hence the fatality of these conditions a long-standing medical challenge. Here, we report the first demonstration of therapeutic efficacy in ATTR amyloidosis via dynamic control of ATTR aggregation and toxicity, enabled by small-molecule organophotocatalysis. Selective incorporation of hydrophilic oxygen atoms into the hydrophobic amyloid core reshapes the aggregation landscape, neutralizing proteotoxicity and mitigating cellular damage. Additionally, this targeted covalent modification significantly reduces in vivo ROS levels, correlating with the observed therapeutic effects in Caenorhabditis elegans, the only experimental model replicating key clinical manifestations of the disease. Docking simulations elucidated the molecular basis of catalyst performance, providing the foundational blueprint for amyloid-neutralizing organophotocatalysis. Collectively, this study provides a scalable approach to overcoming a persistent barrier in amyloidosis therapy.
https://doi.org/10.5061/dryad.1vhhmgr31
General Notes on File Format: The Excel files contain structured formatting elements (e.g., merged cells, section headers, minimal highlighting, and grouped layouts) that were intentionally retained to preserve the logical organization of the biological experiments. Many datasets compile multiple related experimental conditions, replicates, and image-derived measurements within a single sheet. The formatting is used solely to clarify experimental grouping (e.g., treatment conditions, time points, replicates, and figure correspondence) and to maintain traceability between raw images and quantified values.
No calculations depend on embedded formulas or formatting features. All numerical values used for statistical analysis are provided as static entries and can be readily extracted for independent re-analysis.
Raw image files (e.g., spectra, gels, blots, and EM images) are included for transparency and data visibility. Quantitative analyses were performed using the numerical measurements reported in the spreadsheets. The formatting does not alter or constrain access to the underlying raw data.
Detailed experimental procedures and assay descriptions are provided in the associated manuscript. The README defines column headers, abbreviations, symbols, and measurement units necessary for interpretation of the tabulated data.
All datasets correspond directly to specific figures in the associated manuscript, as indicated in the File Description section below.
Column Structure, Abbreviations, and Units
Across datasets, tabular files follow a consistent organizational structure reflecting experimental design, quantitative measurements, and statistical analysis.
Common Column Types
Condition / Treatment – Experimental group identifier
n – Number of independent experimental runs or biological replicates
Time (s, min, h, or d) – Incubation time in seconds (s), minutes (min), hours (h), or days (d)
Concentration (µM or mM) – Compound concentration in micromolar (µM) or millimolar (mM)
Intensity (a.u.) – MALDI-TOF peak intensity or fluorescence intensity reported in arbitrary units
Relative Intensity (%) – Peak intensity normalized to control and expressed as a percentage
Δf (Hz) – Frequency shift measured in Quartz Crystal Microbalance experiments, reported in hertz
Kd (µM) – Dissociation constant in micromolar
Body Bends (/30 s) – Number of body bends per 30 seconds
Mean – Arithmetic mean of measured values
SD – Standard deviation
p-value – Statistical significance value
The Greek symbol Δ used in column headers retains its conventional scientific meaning, indicating a change in the specified parameter. The Greek symbol α denotes experimental treatment parameters as defined in the manuscript.
Measurement units are indicated directly in column headers where applicable. If units differ from those listed above, they are specified explicitly within the corresponding dataset.
Abbreviations
TTR – Transthyretin
Aβ – Amyloid-β
MALDI-TOF-MS – Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry
QCM – Quartz Crystal Microbalance
CBB – Coomassie Brilliant Blue staining
WB – Western blot
ROS – Reactive oxygen species
FFA – Furfuryl alcohol
EM – Electron microscopy
MM/GBSA – Molecular Mechanics/Generalized Born Surface Area
File Description
Movie S1 (MP4 file). Clips of body bending assay for condition 1.
Movie S2 (MP4 file). Clips of body bending assay for condition 2, day 1 (α = 2) of treatment.
Movie S3 (MP4 file). Clips of body bending assay for condition 2, day 3 (α = 4) of treatment.
Dataset S1 (Excel file). Raw MALDI-TOF-MS charts and Fiji peak measurements for initial screening of catalysts (corresponds to Figure 2c).
Dataset S2 (Excel file). Raw MALDI-TOF-MS charts/ Fiji peak measurements for catalyst optimization (corresponds to Figure 2e) and raw MALDI-TOF-MS charts/Fiji peak measurements for photooxygenation under reduced catalyst loadings (corresponds to Figure S6).
Dataset S3 (Excel file). QCM-derived binding curves used to determine dissociation constants (Kd).
Dataset S4 (Excel file). Raw MALDI-TOF-MS charts/Fiji peak measurements for photooxygenation of V30M-TTR (corresponds to Figure S5a) and for photooxygenation of Aβ (corresponds to Figure S5b and S5c).
Dataset S5 (Excel file). Raw MALDI-TOF-MS charts/Fiji peak measurements and/or CBB stained gel images for singlet oxygen trapping using FFA (corresponds to Figure S7a), ROS scavenger assay (corresponds to Figure S7b), and amyloid selectivity tests using tetrameric or aggregated TTR (corresponds to Figures S7c-e).
Dataset S6 (Excel file). Raw MALDI-TOF-MS charts/Fiji peak measurements and CBB or oriole-stained gel images for amyloid selectivity tests using off-target proteins (corresponds to Figure S7f and S7g).
Dataset S7 (Excel file). Raw set of EM images for ATTR fibrils (corresponds to Figure 4a).
Dataset S8 (Excel file). Raw measurements and statistical analyses for cellular rescue assay (corresponds to Figure 4d).
Dataset S9 (Excel file). Raw measurements, images of WB gels, and statistical analyses for photooxygenation in vivo (corresponds to Figures 5b and c).
Dataset S10 (Excel file). Raw measurements and statistical analyses for C. elegans body bending assays (corresponds to Figures 5d and e).
Dataset S11 (Excel file). Raw measurements and statistical analyses for ROS detection assay (corresponds to Figure 5g-i).
Dataset S12 (Mol2 file). Refined WT-TTR23-35 fragment structure and docking simulation results (corresponds to Figures 6a and b).
Dataset S13 (Mol2 file). Refined WT-TTR23-35-ox fragment structure and docking simulation results (corresponds to Figure 6d).
Dataset S14 (Excel file). Raw values for ligand efficiency of binding free energy calculated by MM/GBSA (corresponds to Figure 6c).
Note: Unformatted CSV versions of all tabular datasets are provided alongside the original Excel files. The CSV files correspond directly to the Excel sheets and follow the same tab order as in the original workbooks.
