Anna Szlachcic
University of Wrocław
Binding siteBiophysicsProtein aggregationMutantCytotoxic T cellChemistryPhage displayFGF1ConjugateMonomethyl auristatin ENucleotide exchange factorChaperone (protein)Protein structureCancer researchBiochemistryComputational biologyFibroblast growth factorFibroblast growth factor receptorBiologyCell biologyCancer cell
26Publications
10H-index
1,089Citations
Publications 24
Newest
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 ...
Source
#1Karolina Jendryczko (UWr: University of Wrocław)
#2Julia Chudzian (UWr: University of Wrocław)H-Index: 2
Last. Anna Szlachcic (UWr: University of Wrocław)H-Index: 10
view all 8 authors...
Fibroblast growth factor receptors (FGFRs) are emerging targets for directed cancer therapy. Presented here is a new FGFR1-targeting conjugate, the peptibodyF2, which employs peptibody, a fusion of peptide and the Fc fragment of human IgG as a selective targeting agent and drug carrier. Short peptide based on FGF2 sequence was used to construct a FGFR1-targeting peptibody. We have shown that this peptide ensures specific delivery of peptibodyF2 into FGFR1-expressing cells. In order to use peptib...
Source
#1Anna Szlachcic (UWr: University of Wrocław)H-Index: 10
#2Martyna Sochacka (UWr: University of Wrocław)H-Index: 2
Last. Malgorzata Zakrzewska (UWr: University of Wrocław)H-Index: 17
view all 7 authors...
Fibroblast growth factor 1 (FGF1) has been shown to interact with integrin αvβ3 through a specific binding site, involving Arg35 residue. The FGF1 mutant (R35E) with impaired integrin binding was found to be defective in its proliferative response, although it was still able to interact with FGF receptors (FGFR) and heparin and induce the activation of downstream signaling pathways. Here, we demonstrate that the lack of mitogenic potential of R35E mutant is directly caused by its decreased therm...
3 CitationsSource
#1Magdalena Lipok (UWr: University of Wrocław)H-Index: 1
#2Anna Szlachcic (UWr: University of Wrocław)H-Index: 10
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 5 authors...
: Overexpression of fibroblast growth factor receptor 1 (FGFR1) is a common aberration in lung and breast cancers and has necessitated the design of drugs targeting FGFR1-dependent downstream signaling and FGFR1 ligand binding. To date, the major group of drugs being developed for treatment of FGFR1-dependent cancers are small-molecule tyrosine kinase inhibitors; however, the limited specificity of these drugs has led to increasing attempts to design molecules targeting the extracellular domain ...
6 CitationsSource
#1Julia Chudzian (UWr: University of Wrocław)H-Index: 2
#2Anna Szlachcic (UWr: University of Wrocław)H-Index: 10
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 7 authors...
Fibroblast growth factor 1 (FGF1) and its receptors (FGFRs) regulate crucial biological processes such as cell proliferation and differentiation. Aberrant activation of FGFRs by their ligands can promote tumor growth and angiogenesis in many tumor types, including lung or breast cancer. The development of FGF1-targeting molecules with potential implications for the therapy of FGF1-driven tumors is recently being considered a promising approach in the treatment of cancer. In this study we have us...
2 CitationsSource
#1Karolina Świderska (UWr: University of Wrocław)H-Index: 2
#2Anna Szlachcic (UWr: University of Wrocław)H-Index: 10
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 5 authors...
In the rapidly developing field of targeted cancer therapy there is growing interest towards therapeutics combining two or more compounds to achieve synergistic action and minimize the chance of cancer resistance to treatment. We developed a fibroblast growth factor 2 (FGF2)-conjugate bearing two cytotoxic drugs with independent mode of action: α-amanitin and monomethyl auristatin E. Drugs are covalently attached to the targeting protein in a site-specific manner via maleimide-thiol conjugation ...
7 CitationsSource
#1Janine Kirstein (Leibniz Association)H-Index: 20
#2Kristin Arnsburg (Leibniz Association)H-Index: 6
Last. Nadinath B. Nillegoda (DKFZ: German Cancer Research Center)H-Index: 18
view all 8 authors...
Summary Protein aggregation is enhanced upon exposure to various stress conditions and aging, which suggests that the quality control machinery regulating protein homeostasis could exhibit varied capacities in different stages of organismal lifespan. Recently, an efficient metazoan disaggregase activity was identified in vitro, which requires the Hsp70 chaperone and Hsp110 nucleotide exchange factor, together with single or cooperating J-protein co-chaperones of classes A and B. Here, we describ...
28 CitationsSource
#1K.W. Swiderska (UWr: University of Wrocław)H-Index: 1
#2Anna Szlachcic (UWr: University of Wrocław)H-Index: 10
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 5 authors...
Abstract Recent advances in site-specific protein modification include the increasingly popular incorporation of unnatural amino acid(s) using amber codon, a method developed by Schultz and coworkers. In this study, we employ this technique to introduce propargyllysine (PrK) in human fibroblast growth factor 2 (FGF2). Owing to an alkyne moiety in its side chain, PrK is compatible with Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC). We successfully tested CuAAC-mediated conjugatio...
7 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
view all 6 authors...
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
#1Nadinath B. Nillegoda (DKFZ: German Cancer Research Center)H-Index: 18
#2Antonia Stank (Heidelberg Institute for Theoretical Studies)H-Index: 6
Last. Bernd Bukau (DKFZ: German Cancer Research Center)H-Index: 119
view all 9 authors...
All cells must maintain their proteins in a correctly folded shape to survive. The task of sustaining a healthy set of proteins has increased with the rise of complex life from prokaryotes (such as bacteria) that form simple single-celled organisms to eukaryotes (such as yeast, plants and multicellular animals). As a result of organisms ageing or acquiring genetic mutations, or under stressful conditions such as high temperature, proteins can lose their normal shape and clump together to form “a...
36 CitationsSource