Fig. 6: Putative in situ binding targets of anti-amyloidogenic compounds.

Volcano plots showing peptides with altered abundance after addition of EGCG to a cell lysate (A) and brain lysate (B). Dotted lines indicate the significance threshold |log₂FC| > 1, q-value < 0.05; peptides from α -synuclein are colored in red. (C) Structural fingerprint of α-Synuclein in cell (top) and brain (bottom) lysate. The scale indicates the score per amino acid. The significance threshold of −log₁₀(0.05) × log₂(2) is shown in white, with red indicating higher scores. The more intense the red color, the higher the score. Not significant in gray. Not detected in yellow. D Number of putative targets identified for the indicated compounds in a LiPQuant analysis in cell lysate (LiPQuant score > 2). E Plotted is the percentage of LiPQuant hits for doxycycline (LiPQuant score >2) (red) or background proteome (orange) that were previously identified in a doxycycline pulldown⁵⁸. Enrichment over background was calculated using Fisher’s exact test. F GO enrichment analysis (molecular function) for putative target proteins of the indicated compounds (LiPQuant score > 2). G Significant peptides (orange for EGCG, red for Baicalein) mapped on GRP78 structure (pdb: 3ldp). Small molecule inhibitor 3P1 in cyan. Binding site in purple. H Significant peptide (red) mapped on GLUD1 structure (pdb: 1l1f). ATP binding site extracted from “www.uniport.org” in cyan. I Significant peptide (red) mapped on bovine GLUD1 structure (pdb: 6dhl). ECG in cyan. J The two significant peptides (red) of Cytochrome C in the presence of Baicalein mapped on the Cytochrome C structure (pdb: 1j3s). HEME C in cyan. Significant peptides were defined as those with a LiPQuant score >2.