Chemical Tools for Study of Cell Death and High-throughput Screening

We have a long-standing interest in developing novel tools for the study of cell death; for example, we have recently disclosed a small molecule that induces apoptotic cell death with unparalleled speed.   In addition, we have developed high-end technologies for HTS, with an emphasis on methods that can directly report on compound binding (versus traditional assays that measure enzymatic activity). In this vein we work closely with Professor Brian Cunningham at UIUC and have developed novel photonic crystal methods for the rapid detection of inhibitors of protein-DNA interactions, protein-protein interactions, and for direct detection of small molecules binding to proteins.

Diagram showing Active Sensor, Reference Sensor and Optical gain. Bar chart showing Intensity per Wavelength and another bar chart showing Small molecule binding on Lasing Wavelength per Time.

Related Publications:

  1. 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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  1. A Small Molecule that Induces Intrinsic Pathway Apoptosis with Unparalleled Speed
    Palchaudhuri, R.; Lambrecht, M. J.; Botham, R. C.; Partlow, K. C.; Van Ham, T. J.; Putt, K. S.; Nguyen, L. T.; Kim, S.-H.; Peterson, R. T.; Fan, T. M.; Hergenrother, P. J. 
    Cell Reports 2015, 13, 2027-2036.

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  1. Detection of Protein-Small Molecule Binding Using a Self-Referencing External Cavity Laser Biosensor​
    Zhang, M.; Peh, J.; Hergenrother, P. J.; Cunningham, B. T.
    J. Am. Chem. Soc. 2014, 136, 5840-5843.

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  1. External Cavity Laser Biosensor
    Ge, C.; Lu, M.; George, S.; Flood, T. A.; Wagner, C.; Zheng, J.; Pokhriyal, A.; Eden, J. G.; Hergenrother, P. J.; Cunningham, B. T.
    Lab Chip 2013, 13, 1247-1256.

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    UIUC News Highlight
  1. Whole Cell Microtubule Analysis by Flow Cytometry
    Morrison, K.C.; Hergenrother, P. J.  
    Anal. Biochem. 2012, 420, 26-32. 

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  1. Transcript Profiling and RNA Interference as Tools to Identify Small Molecule Mechanisms and Therapeutic Potential
    Palchaudhuri, R.; Hergenrother, P. J.  
    ACS Chem. Biol. 2011, 6, 21-33. 

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  1. High-Throughput Screening for Modulators of Protein-Protein Interactions: Use of Photonic Crystal Biosensors and Complementary Technologies
    Heeres, J. T.; Hergenrother, P. J.
    Chem. Soc. Rev. 2011, 40, 4398-4410.

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  1. Preparation of the Caspase-3/7 Substrate Ac-DEVD-pNA by Solution-Phase Peptide Synthesis
    Peterson, Q. P.; Goode, D. R.; West, D. C.; Botham, R. C.; Hergenrother, P. J. 
    Nature Protocols 2010, 5, 294-302.

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  1. Identifying Modulators of Protein-Protein Interactions Using Photonic Crystal Biosensors
    Heeres, J. T.; Kim, S.-H.; Leslie, B. J.; Lidstone, E. A.; Cunningham, B. T.; Hergenrother, P. J.
    J. Am. Chem. Soc. 2009, 131, 18202-18203.

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    BioPhotonics Highlight
  1. A General Method for Discovering Inhibitors of Protein-DNA Interactions Using Photonic Crystal Biosensors
    Chan, L. C.; Pineda, M.; Heeres, J. T.; Hergenrother, P. J.; Cunningham, B. T.
    ACS Chem. Biol. 2008, 3, 437-448.

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    About the Authors
    RSC News Highlight
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    Medical News Today Highlight
    Photonics.com Highlight
  1. Identification of the Cellular Targets of Bioactive Small Organic Molecules Using Affinity Reagents 
    Leslie, B. J.; Hergenrother, P. J. 
    Chem. Soc. Rev. 2008, 37, 1347-1360.

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  1. Obtaining and screening compound collections: A user’s guide and a call to chemists
    Hergenrother, P. J.  
    Curr. Opin. Chem. Biol. 2006, 10, 213-218.

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  1. Direct Quantitation of Poly(ADP-Ribose) Polymerase (PARP) Activity as a Method to Distinguish Necrotic and Apoptotic Death in Cell and Tissue Samples
    Putt, K. S.; Beilman, G. J.; Hergenrother, P. J.
    ChemBioChem 2005, 6, 53-55. 

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  1. A non-radiometric, high-throughput assay for poly(ADP-ribose) glycohydrolase (PARG): Application to inhibitor identification and evaluation
    Putt, K. S.; Hergenrother, P. J. 
    Anal. Biochem. 2004, 333, 256-264. 

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  1. An Enzymatic Assay for Poly(ADP-Ribose) Polymerase (PARP-1) via the Chemical Quantitation of NAD+: Application to the High-Throughput Screening of Small Molecules as Potential Inhibitors
    Putt, K. S.; Hergenrother, P. J. 
    Anal. Biochem. 2004, 326, 78-86. 

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Procaspase-3 Activation
PARG Inhibition
Activation by NQO1
ErSO-related Compounds
Other Anticancer Compounds