Nanoscale, automated, high throughput synthesis and screening for the accelerated discovery of protein modifiers.

ABSTRACT: Hit finding in early drug discovery is often based on high throughput screening (HTS) of existing and historical compound libraries, which can limit chemical diversity, is time-consuming, very costly, and environmentally not sustainable. On-the-fly compound synthesis and in situ screening in a highly miniaturized and automated format has the potential to greatly reduce the medicinal chemistry environmental footprint. Here, we used acoustic dispensing technology to synthesize a library in a 1536 well format based on the Groebcke-Blackburn-Bienaymé reaction (GBB-3CR) on a nanomole scale. The unpurified library was screened by differential scanning fluorimetry (DSF) and cross-validated using microscale thermophoresis (MST) against the oncogenic protein-protein interaction menin-MLL. Se

SUBMITTER: Gao K 

PROVIDER: S-EPMC8152715 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature