Figure 1

HT-CM-SPR Screening of αSyn. (a) The HT-CM-SPR process: Monomeric αSyn analyte floats over the array surface in screening buffer to allow binding events to occur. SPR imaging enables the detection of binding events. (b) SPR Test Screening Results: The upper two panels show images of color coded SPR signals obtained during HT-CM-SPR of αSyn under optimized screening conditions against individual representative microarrays comprised of (1) a fragment microarray containing 3,070 fragments (out of 23,000 fragments present in the entire screened NovAliX chemical microarray library) spotted in triplicate along a diagonal and (2) a lead-like microarray of 9,216 lead-like compounds (out of 91,000 lead-like compounds present in the entire screened NovAliX chemical microarray library) individually spotted. The lead-like compounds are derived from combinatorial synthesis approaches with each row and column on the microarrays consisting of a common fragment in combination with 96 other diversities. In these fingerprint representations of the microarrays each spot is representative of a separate small molecule tethered to the array with the ___location on the chip reflected by the ___location on the fingerprint and the color representing the intensity of signal for that spot (color ranging from low shifts (blue) to high (red) signals). The lower panels 3 and 4 show reproducibility of duplicate screening experiments for chemical microarrays shown in panels 1 and 2. The reproducibility of these subsets of compounds is representative of results obtained for the entire NovAliX chemical microarray library with (3) triplicates of 3,070 fragments and for (4) individual 9,216 lead-like compounds immobilized. In these scatter plots, each spot compares the signal strength measured for the microarray samples in each of the independent array experiments with signals from one replicate experiment indicated on the Y-axis and that of the other experiment represented on the X-axis.