A DNA-encoded library for the identification of natural product binders that modulate poly (ADP-ribose) polymerase 1, a validated anti-cancer target

摘要: Natural products have been an invaluable source of drug discovery, but their targets remain largely unknown. enriched DNA-encoded chemical libraries (nDELs) empower the researchers to rapidly and economically screen numerous natural against various protein targets, therefore promote elucidation molecular mechanisms. In this work, we used poly (ADP-ribose) polymerase 1 (PARP1), as example explore usage nDEL for functional selection. We late-stage modification approach label three positive binders with unique DNA barcodes, whose dissociation constants range from sub-micromolar micromolar. The selection criterion was set up according enrichment these controls. Five selected by directly bind PARP1 in SPR, among which luteolin exhibits highest inhibitory activity PARP1. Moreover, selectively induces accumulation double-strand breaks G2/M phase arrest BRCA-deficient cells. All findings investigations on support that inhibition is one mechanisms its anti-cancer activity.