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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 pyrrolidine, (2R,3R,4S)-1-(benzyloxycarbonyl)-2-(hydroxymethyl)pyrrolidine-3,4-diol 3,4-O-isopropylidene acetal. This starting pyrrolidine was phosphorylated, coupled to adenosine 5'-monophosphate, and deprotected, yielding the title inhibitor ADP-HPD. ADP-HDP was shown to inhibit the activity of poly(ADP-ribose) glycohydrolase by 50% (IC50) at 0.12 microM, a value 1000-times lower than the IC50 of the product, ADP-ribose. The NAD glycohydrolase from Bungarus fasciatus venom was less sensitive to inhibition by ADP-HPD, exhibiting an IC50 of 260 microM. ADP-HPD did not inhibit either poly(ADP-ribose) polymerase or NAD:arginine mono(ADP-ribosyl)-transferase A at inhibitor concentrations up to 1 mM. At low ADP-HPD concentration, inhibition was therefore shown to be highly specific for poly(ADP-ribose) glycohydrolase, the hydrolytic enzyme in the metabolism of ADP-ribose polymers.
J T Slama, and
N Aboul-Ela, and
D M Goli, and
B V Cheesman, and
A M Simmons, and
M K Jacobson
September 2003,
Journal of medicinal chemistry,
J T Slama, and
N Aboul-Ela, and
D M Goli, and
B V Cheesman, and
A M Simmons, and
M K Jacobson
May 1998,
Biochemistry,
J T Slama, and
N Aboul-Ela, and
D M Goli, and
B V Cheesman, and
A M Simmons, and
M K Jacobson
January 1976,
Archives of biochemistry and biophysics,
J T Slama, and
N Aboul-Ela, and
D M Goli, and
B V Cheesman, and
A M Simmons, and
M K Jacobson
August 1988,
Cancer research,
J T Slama, and
N Aboul-Ela, and
D M Goli, and
B V Cheesman, and
A M Simmons, and
M K Jacobson
April 2007,
Biochemical and biophysical research communications,
J T Slama, and
N Aboul-Ela, and
D M Goli, and
B V Cheesman, and
A M Simmons, and
M K Jacobson
January 1978,
Biochemical Society transactions,
J T Slama, and
N Aboul-Ela, and
D M Goli, and
B V Cheesman, and
A M Simmons, and
M K Jacobson
March 1988,
Biochemistry international,
J T Slama, and
N Aboul-Ela, and
D M Goli, and
B V Cheesman, and
A M Simmons, and
M K Jacobson
April 2005,
Cellular and molecular life sciences : CMLS,
J T Slama, and
N Aboul-Ela, and
D M Goli, and
B V Cheesman, and
A M Simmons, and
M K Jacobson
March 2012,
ACS chemical biology,
J T Slama, and
N Aboul-Ela, and
D M Goli, and
B V Cheesman, and
A M Simmons, and
M K Jacobson
May 1977,
Experimental cell research,
