160711-63-7Relevant academic research and scientific papers
SAR analysis of adenosine diphosphate (hydroxymethyl)pyrrolidinediol inhibition of poly(ADP-ribose) glycohydrolase
Koh, David W.,Coyle, Donna L.,Mehta, Nimish,Ramsinghani, Sushma,Kim, Hyuntae,Slama, James T.,Jacobson, Myron K.
, p. 4322 - 4332 (2007/10/03)
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.
Synthesis of (2R,3R,4S)-2-hydroxymethylpyrrolidine-3,4-diol from (2S)-3,4-dehydroproline derivatives
Goli, Deepa M.,Cheesman, Bruce V.,Hassan, Mohamed E.,Lodaya, Rita,Slama, James T.
, p. 219 - 242 (2007/10/02)
(2R,3R,4S)-2-Hydroxymethylpyrrolidine-3,4-diol (1,4-dideoxy-1,4-imino-D-ribitol) was synthesized in five steps from N-protected (2S)-3,4-dehydroproline methyl esters.The stereoselective reaction of osmium tetraoxide with dehydroproline derivatives gave hi
