"We offer a multidisciplinary approach to in vitro and cellular assays development and adaptation as well as testing compounds of interest with subsequent advanced analyses of interaction target protein – ligand."

Offer

Know-how & Technologies

- We use iBodies for reveling binders/receptors/enzymes of biologically active compounds with unknown targets

- We set up the stochastic modification of those active small molecules to attach the handle to all possible sites on small mollecules, conjugate it to iBodies and after pull-down we identify proteins using mass spectrometry

- We routinely use iBody against GCPII (PSMA), FAP, aspartic proteases, His-tagged proteins and many others are in development

"From ligands of proteases to future first-class early lead compounds."

Content of Research

- In the viral proteases research, we integrate the tools of classical biochemistry and structural biology with methods of cellular and molecular biology for in house development of in vitro and cell-based enzymological assays for search of early lead compounds with non-canonical mechanisms of action.

- In the field of proteases participating in cancer development, we characterized Prostate specific membrane antigen (PSMA) and fibroblast activated protein (FAP) in terms of 3D structure, substrate specificity and inhibitor design.

- We study viral proteases is focused mainly to HIV, Zika and Dengue NS2B-NS3 proteins as models for proteases autoactivation and activity modulation. We also study proteases involved in malignancies (PSMA, FAP and others).

- We develop novel assays for enzyme detection and characterization.

Key Research Equipment

Konvalinka’s lab is a joint laboratory between the Department of Proteases of Human Pathogens at the Institute of Organic Chemistry and Biochemistry of the Academy of Science (IOCB) and Department of Biochemistry. Extensive set of instrumentation at IOCB is available to interested collaborators, including state of the art FPLC instrument, protein microcalorimetry, SPR, qPCR equipment, protein crystallization and others.

Partnerships & Collaborations

Achievements

- Šimon, P., Knedlík, T., Blažková, K., Dvořáková, P., Březinová, A., Kostka. L., Šubr, V., Konvalinka, J. and Šácha, P. (2018) Identification of Protein Targets of Bioactive Small Molecules Using Randomly Photomodified Probes, ACS Chem. Biol. 13, 3333–3342

- Humpolíčková, J., Weber, J., Starková, J., Mašínová, E., Günterová, J., Flaisigová, I., Konvalinka, J.,and Majerová, T. (2018) Inhibition of the precursor and mature forms of HIV-1 protease as a tool for drug evaluation, Scientific Reports 8, 10438

- Tretyachenko V, Vymetal J, Bednarova L, Kopecky V, Jr., Hofbauerova K, Jindrova H, Hubalek M, Soucek R, Konvalinka J, Vondrasek J, Hlouchova K (2017). Random protein sequences can form defined secondary structures and are well-tolerated in vivo. Sci Rep.7, 15449

- Dvořáková P, Bušek P, Knedlík T, Schimer J, Etrych T, Kostka L, Stollinová Šromová L, Šubr V, Šácha P, Šedo A, Konvalinka J. (2017) Inhibitor-Decorated Polymer Conjugates Targeting Fibroblast Activation Protein. J Med Chem. 60, 8385–8393

- Machara A., Lux V., Kožíšek M., Grantz Šašková K., Štěpánek O., Kotora M., Parkan K., Pávová M., Glass B., Sehr P., Lewis J., Müller B., Kräusslich H.G., Konvalinka J. (2016) Specific Inhibitors of HIV Capsid Assembly Binding to the C-Terminal Domain of the Capsid Protein: Evaluation of 2-Arylquinazolines as Potential Antiviral Compounds. Journal of Medicinal Chemistry 59: 545–558

- Šácha P., Knedlík T., Schimer J., Tykvart J., Parolek J., Navrátil V., Dvořáková P., Sedlák F., Ulbrich K., Strohalm J., Majer P., Šubr V., Konvalinka J. (2016) iBodies: modular synthetic antibody mimetics based on hydrophilic polymers decorated with functional moieties. Angewandte Chemie International Edition, Online: January 8

- Vorlová B., Nachtigallová D., Jirásková-Vaníčková J., Ajani H., Jansa P., Řezáč J., Fanfrlík J., Otyepka M., Hobza P., Konvalinka J., Lepšík M. (2015) Malonate-based inhibitors of mammalian serine racemase: Kinetic characterization and structure-based computational study. European Journal of Medicinal Chemistry 89: 189–197

- Schimer J., Pávová M., Anders M., Pachl P., Šácha P., Cígler P., Weber J., Majer P., Řezáčová P., Krausslich H.G., Muller B., Konvalinka J. (2015) Triggering HIV polyprotein processing by light using rapid photodegradation of a tight-binding protease inhibitor. Nature Communications 6: 6461

- Tykvart J., Bařinka C., Svoboda M., Navrátil V., Souček R., Hradílek M., Šácha P., Lubkowski J., Konvalinka J. (2015) Structural and biochemical characterization of human N-acetylated alpha-linked acidic dipeptidase-like (NAALADase L) protein, a novel aminopeptidase from human intestine. Journal of Biological Chemistry 290: 11321–11336

- Tykvart J., Schimer J., Jančařík A., Bařinková J., Navrátil V., Starková J., Šrámková K., Konvalinka J., Majer P., Šácha P. (2015) Design of Highly Potent Urea-Based, Exosite-Binding Inhibitors Selective for Glutamate Carboxypeptidase II. Journal of Medicinal Chemistry 58: 4357–4363

Are you interested in this expertisa?

Please contact CPPT UK

Web: www.cppt.cuni.cz/

Mail: transfer@cuni.cz

Tel.: +420 224 491 255

Experts and their department

Assoc. Prof. RNDr. Jan Konvalinka, CSc.

Department of Biochemistry

Web: https://twitter.com/konvalinka_lab