Discovery of an NAD⁺ analogue with enhanced specificity for PARP1.

ABSTRACT: Among various protein posttranslational modifiers, poly-ADP-ribose polymerase 1 (PARP1) is a key player for regulating numerous cellular processes and events through enzymatic attachments of target proteins with ADP-ribose units donated by nicotinamide adenine dinucleotide (NAD⁺). Human PARP1 is involved in the pathogenesis and progression of many diseases. PARP1 inhibitors have received approvals for cancer treatment. Despite these successes, our understanding about PARP1 remains limited, partially due to the presence of various ADP-ribosylation reactions catalyzed by other PARPs and their overlapped cellular functions. Here we report a synthetic NAD⁺ featuring an adenosyl 3'-azido substitution. Acting as an ADP-ribose donor with high activity and specificity for hum

SUBMITTER: Zhang XN 

PROVIDER: S-EPMC8848837 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature