148252-71-5

Upstream product

• 1053262-99-9 (3aR,4R,6aS)-2,2-Dimethyl-4-phosphonooxymethyl-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylic acid benzyl ester 
• 111265-96-4 (2R,3R,4S)-1-(benzyloxycarbonyl)-2-(hydroxymethyl)pyrrolidine-3,4-diol 3,4-O-isopropylidene acetal 

Downstream Products

• 1055041-51-4 C₃₀H₃₆N₆O₁₄P₂ 
• 208658-24-6 (2R,3R,4S)-2-[(phosphooxy)methyl]pyrrolidine-3,4-diol 

Relevant academic research and scientific papers

Specific inhibition of poly(ADP-ribose) glycohydrolase by adenosine diphosphate (hydroxymethyl)pyrrolidinediol

Adenosine diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD), an NH analog of ADP-ribose, was chemically synthesized and shown to be a potent and specific inhibitor of poly-(ADP-ribose) glycohydrolase. The synthetic starting material was the protected p

SAR analysis of adenosine diphosphate (hydroxymethyl)pyrrolidinediol inhibition of poly(ADP-ribose) glycohydrolase

Polyadenosine diphosphoribose glycohydrolase (PARG) catalyzes the intracellular hydrolysis of adenosine diphosphoribose polymers. Because structure-activity data are lacking for PARG, the specific inhibitor adenosine diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD) was utilized to determine the effects of structure on inhibitor potency using PARG isolated from bovine thymus (bPARG) and recombinant bovine PARG catalytic fragment (rPARG-CF). Both enzymes were strongly inhibited by submicromolar levels of ADP-HPD, but ADP and the phosphorylated pyrrolidine displayed no activity. Utilizing ADP-HPD analogues containing 2-, N6, or 8-adenosyl substituents or guanine instead of adenine, the importance of adenine ring recognition as well as a correlation between loss of PARG inhibition and the length and bulkiness of 8-adenosyl substituents was shown. Utilization of ADP-HPD analogues lacking one or both pyrrolidine cis-hydroxyls demonstrated their importance for inhibitor binding. Last, the similarity between naturally occurring bPARG and heterologously expressed rPARG-CF was demonstrated. Therefore, readily available rPARG-CF is suitable for use in future studies to determine the structural aspects of PARG.