Mateusz Adam Krzyscik
University of Wrocław
CytotoxicityLigand (biochemistry)BiophysicsInternalizationCytotoxic T cellSortaseReceptorChemistryFGF1ConjugateGrowth factorSortase ACysteineMonomethyl auristatin EEndocytosisFibroblast growth factor receptor 1Cancer researchBiochemistryFibroblast growth factorCell cultureFibroblast growth factor receptorCell biologyCancer cell
Publications 9
#1Natalia Porębska (UWr: University of Wrocław)H-Index: 3
#2Marta Pozniak (UWr: University of Wrocław)H-Index: 1
Last. Lukasz Opalinski (UWr: University of Wrocław)H-Index: 3
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Abstract Fibroblast growth factor receptors (FGFRs) are integral membrane proteins involved in various biological processes including proliferation, migration and apoptosis. There are a number of regulatory mechanisms of FGFR signaling, which tightly control the specificity and duration of transmitted signals. The effect of the FGFRs spatial distribution in the plasma membrane on receptor-dependent functions is still largely unknown. We have demonstrated that oligomerization of FGF1 with coiled-...
Cancer is currently the second most common cause of death worldwide. The hallmark of cancer cells is the presence of specific marker proteins such as growth factor receptors on their surface. This feature enables development of highly selective therapeutics, the protein bioconjugates, composed of targeting proteins (antibodies or receptor ligands) connected to highly cytotoxic drugs by a specific linker. Due to very high affinity and selectivity of targeting proteins the bioconjugates recognize ...
#1Marta Pozniak (UWr: University of Wrocław)H-Index: 1
#2Aleksandra Sokolowska-Wedzina (UWr: University of Wrocław)H-Index: 7
Last. Lukasz Opalinski (UWr: University of Wrocław)H-Index: 3
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Fibroblast growth factor receptor 1 (FGFR1) transmits signals through the plasma membrane regulating essential cellular processes like division, motility, metabolism and death. Overexpression of FGFR1 is observed in numerous tumors and thus constitutes an attractive molecular target for selective cancer treatment. Targeted anti-cancer therapies aim for the precise delivery of drugs into cancer cells, sparing the healthy ones and thus limiting unwanted side effects. One of the key steps in target...
2 CitationsSource
In spite of significant progress in the field of targeted anticancer therapy, the FDA has approved only five ADC-based drugs. Hence the search for new targeted anticancer agents is an unfulfilled n...
2 CitationsSource
#1Daria Nawrocka (UWr: University of Wrocław)H-Index: 1
#2Mateusz Adam Krzyscik (UWr: University of Wrocław)H-Index: 4
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
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Fibroblast growth factor 2 (FGF2) is a heparin-binding growth factor with broad mitogenic and cell survival activities. Its effector functions are induced upon the formation of 2:2 FGF2:FGFR1 tetrameric complex. To facilitate receptor activation, and therefore, to improve the FGF2 biological properties, we preorganized dimeric ligand by a covalent linkage of two FGF2 molecules. Mutations of the FGF2 WT protein were designed to obtain variants with a single surface-exposed reactive cysteine for t...
2 CitationsSource
The targeted therapies are rapidly evolving modalities of cancer treatment. The largest group of currently developed biopharmaceuticals are antibody-drug conjugates (ADCs). Here, we developed a new modular strategy for the generation of cytotoxic bioconjugates, containing a homodimer of targeting protein and two highly-potent anticancer drugs with distinct mechanisms of action. Instead of antibody, we applied human fibroblast growth factor 2 (FGF2) as a targeting protein. We produced a conjugate...
4 CitationsSource
#1Lukas Balek (Masaryk University)H-Index: 10
#2Marcela Buchtová (Masaryk University)H-Index: 19
Last. Pavel Krejci (Masaryk University)H-Index: 32
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Abstract The blocking of specific protein-protein interactions using nanoparticles is an emerging alternative to small molecule-based therapeutic interventions. However, the nanoparticles designed as “artificial proteins” generally require modification of their surface with (bio)organic molecules and/or polymers to ensure their selectivity and specificity of action. Here, we show that nanosized diamond crystals (nanodiamonds, NDs) without any synthetically installed (bio)organic interface enable...
10 CitationsSource
#1Mateusz Adam Krzyscik (UWr: University of Wrocław)H-Index: 4
#2Malgorzata Zakrzewska (UWr: University of Wrocław)H-Index: 17
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
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Antibody–drug conjugates (ADCs) are a new class of anticancer therapeutics that combine the selectivity of targeted treatment, ensured by monoclonal antibodies, with the potency of the cytotoxic agent. Here, we applied an analogous approach, but instead of an antibody, we used fibroblast growth factor 2 (FGF2). FGF2 is a natural ligand of fibroblast growth factor receptor 1 (FGFR1), a cell-surface receptor reported to be overexpressed in several types of tumors. We developed and characterized FG...
6 CitationsSource
#1Michal Lobocki (UWr: University of Wrocław)H-Index: 3
#2Malgorzata Zakrzewska (UWr: University of Wrocław)H-Index: 17
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
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Site-specific conjugation is a leading trend in the development of protein conjugates, including antibody–drug conjugates (ADCs), suitable for targeted cancer therapy. Here, we present a very efficient strategy for specific attachment of a cytotoxic drug to fibroblast growth factor 1 (FGF1), a natural ligand of FGF receptors (FGFRs), which are over-expressed in several types of lung, breast, and gastric cancers and are therefore an attractive molecular target. Recently, we showed that FGF1 fused...
9 CitationsSource