Fig. 4.

Positive, colloidal and non-specific binding molecules from focused HTS. (a) Molecule numbers 3 (i) and 16 (ii) exhibit ‘positive’ (specific) binding to Aβ40 monomer (purple peaks) according to the ESI-IMS–MS classification system and negative stain TEM images of Aβ40 incubated with 10:1 molar ratios of molecule: Aβ40 for 5 days in 200 mM ammonium acetate buffer, pH 6.8 (25 °C, quiescent) show the absence of fibrils after incubation. (b) Compound 9 (i) exhibits colloidal binding to itself (peaks denoted nL where n is the number of small molecules present in the aggregate) and to Aβ40 + nL (green peaks). (c) Compounds 15 (i) and 17 (ii) exhibit non-specific binding to Aβ40 (pink peaks). Compounds 9, 15 and 17 fail to prevent fibrillation of Aβ40 (scale bar in nm is indicated at the foot of each TEM image). Circles in ESI-IMS–MS Driftscope images indicate the number of small molecules bound to each ion.