Prof. RNDr. Jan Konvalinka, CSc.
+420 220 183 218
Vybrané publikace
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)
Nejnovější publikace
Structural and Thermodynamic Analysis of the Resistance Development to Pimodivir (VX-787), the Clinical Inhibitor of Cap Binding to PB2 Subunit of Influenza A Polymerase
Molecules 26 (4): 1007 (2021)
Structural characterization of the interaction between the C-terminal domain of the influenza polymerase PA subunit and an optimized small peptide inhibitor
Antiviral Research 185: 104971 (2021)
Unraveling the anti-influenza effect of flavonoids: Experimental validation of luteolin and its congeners as potent influenza endonuclease inhibitors
European Journal of Medicinal Chemistry 208: 112754 (2020)
Identification of Novel Carbonic Anhydrase IX Inhibitors Using High-Throughput Screening of Pooled Compound Libraries by DNA-Linked Inhibitor Antibody Assay (DIANA)
SLAS Discovery 25 (9): 1026-1037 (2020)