PARG INHIBITION

Poly(ADP-ribose) (PAR) is synthesized by the enzyme PARP-1 in response to DNA damage. The enzyme poly(ADP-ribose)glycohydrolase (PARG) cleaves PAR down to smaller PAR chains and ultimately to ADP-ribose. Inhibitors of PARP-1 and PARG thus can disrupt the normal process of DNA damage repair, and therefore have potential as antitumor drugs either alone or in combination with DNA damaging agents. We are actively synthesizing novel PARG substrates and inhibitors and using these compounds as tools to interrogate PARG inhibition as an anticancer strategy.

PAR Metabolism

Related Publications:

144.

Structural analyses of NudT16–ADP-ribose complexes direct rational design of mutants with improved processing of poly(ADP-ribosyl)ated proteins

Thirawatananond, P.; McPherson, R. L.; Malhi, J.; Nathan, S.; Lambrecht, M.J.; Brichacek, M.; Hergenrother, P.J.; Leung, A.K.L.; Gabelli, S.B.

Sci. Reports20199, 5940

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140.

(ADP-ribosyl)hydrolases: Structural basis for differential substrate recognition and inhibition

Rack, J.G.M.; Ariza, A.; Drown, B. S.; Henfrey, C.; Shirai, T.; Hergenrother, P. J.; Ahel, I.

Cell Chem. Biol. 2018, 25, 1533-1546

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138.

Monitoring poly(ADP-ribosyl)glycohydrolase activity with a continuous fluorescent substrate

Drown, B. S.; Shirai, T.; Rack, J.G.M.; Ahel, I.; Hergenrother, P. J.

Cell Chem. Biol. 2018, 25, 1562-1570

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110.

Synthesis of Dimeric ADP-Ribose and Its Structure with Human Poly(ADP-Ribose) Glycohydrolase

Lambrecht, M. J.; Brichacek, M.; Barkauskaite, E.; Ariza, A.; Ahel, I.; Hergenrother, P. J.  

J. Am. Chem. Soc. 2015137, 3558-3564.

 

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91.

Structure and Mechanism of a Canonical Poly(ADP-Ribose) Glycohydrolase

Dunstan, M. S.; Barkauskaite, E.; Lafite, P.; Knezevic, C. E.; Brassington, A.; Ahel, M.; Hergenrother, P. J.; Leys, D.; Ahel, I. 

Nat. Commun. 2012, 3, 878.

 

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86.

Selective Small Molecule Inhibition of Poly(ADP-Ribose) Glycohydrolase (PARG)

Finch, K. E.; Knezevic, C. E.; Nottbohm, A. C.; Partlow, K. C.; Hergenrother, P. J.

ACS Chem. Biol. 2012, 7, 563-570.

 

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Meet the Authors

49.

Poly(ADP-Ribose) Makes a Date with Death

Heeres, J. T.; Hergenrother, P. J.

Curr. Opin. Chem. Biol. 2007, 11, 644-653.

 

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44.

The Promises and Pitfalls of Small-Molecule Inhibition of Poly(ADP-Ribose) Glycohydrolase (PARG)

Nottbohm, A. C.; Hergenrother, P. J.

Drug Discovery Research: New Frontiers in the Post-Genomic Era 2007, 163-185.

 

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Professor Paul J. Hergenrother

hergenro@illinois.edu

261 Roger Adams Lab

600 S. Mathews Avenue

Urbana, IL 61802

The Chemistry Department at the University of Illinois

Copyright © 2014 The Hergenrother Group

Julie Bass

Administrative Assistant

jlbass2@illinois.edu

245 Roger Adams Lab

#PJHteam