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Polymer therapeutics with a coiled coil motif targeted against murine BCL1 leukemia
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SYSNO ASEP 0390945 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Polymer therapeutics with a coiled coil motif targeted against murine BCL1 leukemia Author(s) Pola, Robert (UMCH-V) RID, ORCID
Laga, Richard (UMCH-V) RID, ORCID
Ulbrich, Karel (UMCH-V) RID
Sieglová, Irena (UMG-J)
Král, Vlastimil (UMG-J) RID
Fábry, Milan (UMG-J) RID
Kabešová, Martina (MBU-M) RID
Kovář, Marek (MBU-M) RID, ORCID
Pechar, Michal (UMCH-V) RID, ORCIDSource Title Biomacromolecules. - : American Chemical Society - ISSN 1525-7797
Roč. 14, č. 3 (2013), s. 881-889Number of pages 9 s. Language eng - English Country US - United States Keywords coiled coil ; polymer therapeutics ; scFv Subject RIV CD - Macromolecular Chemistry Subject RIV - cooperation Institute of Microbiology - Immunology
Institute of Molecular Genetics - Genetics ; Molecular BiologyR&D Projects GAP301/11/0325 GA ČR - Czech Science Foundation (CSF) IAAX00500803 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR) Institutional support UMCH-V - RVO:61389013 ; MBU-M - RVO:61388971 ; UMG-J - RVO:68378050 CEZ AV0Z50520514 - UMG-J (2005-2011) UT WOS 000316044700034 DOI 10.1021/bm3019592 Annotation The specificity of polymer conjugates based on N-(2-hydroxypropyl)methacrylamide (HPMA) bearing cytostatic drugs for cancer cells could be significantly increased by the incorporation of a suitable targeting ligand, such as a monoclonal antibody (mAb). However, direct binding of the protein to the polymer carrier could cause considerable problems, such as decreasing the binding capacity of mAb to its target. Here, we introduce a novel strategy of joining a targeting moiety to a polymeric conjugate with cytostatic drug. The scFv of B1 mAb (specific for BCL1 leukemia cells) was tagged with peptide K ((VAALKEK)4). Peptide E ((VAALEKE)4), which forms a stable coiled coil structure heterodimer with peptide K, was assembled with the HPMA copolymers bearing doxorubicin. Such targeted polymeric conjugates possess very selective and high binding activity toward BCL1 cells. Similarly, targeted polymeric conjugates exert approximately 100 times higher cytostatic activity toward BCL1 cells in comparison to nontargeted conjugates in vitro. At the same time, the conjugates have comparable and rather low cytostatic activity for 38C13 cells, which are used as a negative control, in vitro. Workplace Institute of Macromolecular Chemistry Contact Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Year of Publishing 2014
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