Virtual screening for plant PARP inhibitors – what can be learned from human PARP inhibitors?
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KeywordsAbiotic Stress Knowledge Transfer Virtual Screening Exact Role Potential Plant
The functions of Poly(ADP-ribose) polymerase enzymes (PARPs) in general are best studied based on human PARP-1 (HsPARP-1). HsPARP-1 is well investigated because pharmacological modulation of its activity modulates DNA-binding of antitumor drugs . In contrast to human PARP enzymes, the exact role of PARPs in plants remains to be elucidated. Different stresses activate plant PARP enzymes to mediate DNA repair and (programmed) cell death whereas the addition of PARP inhibitors decreases the degree of cell death . Therefore, the development of plant PARP inhibitors might be a way to increase the tolerance against abiotic stress.
Knowing the differences of the human and plant screening routes, predictions of the applicability of that multi-step process on a commercial database have been explored. Finally, the developed virtual screening route has been applied to screen a commercial database for AtPARP-1 inhibitors. From 20 compounds tested so far in vitro, 13 show inhibitory effects.
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