Selected papers

Identification of Protein Targets of Bioactive Small Molecules Using Randomly Photomodified Probes
Identification of Protein Targets of Bioactive Small Molecules Using Randomly Photomodified Probes
ACS Chemical Biology 13 (12): 3333-3342 (2018)
Identifying protein targets of bioactive small molecules often requires complex, lengthy development of affinity probes. We present a method for stochastic modification of small molecules of interest with a photoactivatable phenyldiazirine linker. The resulting isomeric mixture is conjugated to a hydrophilic copolymer decorated with biotin and a fluorophore. We validated this approach using known inhibitors of several medicinally relevant enzymes. At least a portion of the stochastic derivatives retained their binding to the target, enabling target visualization, isolation, and identification. Moreover, the mix of stochastic probes could be separated into fractions and tested for binding affinity. The structure of the active probe could be determined and the probe resynthesized to improve binding efficiency. Our approach can thus enable rapid target isolation, identification, and visualization, while providing information required for subsequent synthesis of an optimized probe.
DNA-linked Inhibitor Antibody Assay (DIANA) for sensitive and selective enzyme detection and inhibitor screening
Nucleic Acids Research 45 (2): e10 (2017)
DNA-linked inhibitor antibody assay (DIANA) as a new method for screening influenza neuraminidase inhibitors
Biochemical Journal 475 (23): 3847-3860 (2018)
iBodies: Modular Synthetic Antibody Mimetics Based on Hydrophilic Polymers Decorated with Functional Moieties
Angewandte Chemie International Edition 55 (7): 2356-2360 (2016)

Latest publications

Viral proteases as therapeutic targets
Molecular Aspects of Medicine 88: 101159 (2022)
Thermodynamic and structural characterization of an optimized peptide-based inhibitor of the influenza polymerase PA-PB1 subunit interaction
Antiviral Research 208: 105449 (2022)
Predicting Effects of Site-Directed Mutagenesis on Enzyme Kinetics by QM/MM and QM Calculations: A Case of Glutamate Carboxypeptidase II
Journal of Physical Chemistry B 126 (1): 132–143 (2022)