About: Polymer therapeutics with a coiled coil motif targeted against murine BCL1 leukemia     Goto   Sponge   NotDistinct   Permalink

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  • 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.
  • 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. (en)
Title
  • Polymer therapeutics with a coiled coil motif targeted against murine BCL1 leukemia
  • Polymer therapeutics with a coiled coil motif targeted against murine BCL1 leukemia (en)
skos:prefLabel
  • Polymer therapeutics with a coiled coil motif targeted against murine BCL1 leukemia
  • Polymer therapeutics with a coiled coil motif targeted against murine BCL1 leukemia (en)
skos:notation
  • RIV/68378050:_____/13:00390945!RIV14-AV0-68378050
http://linked.open...avai/predkladatel
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I, P(GAP301/11/0325), P(IAAX00500803), Z(AV0Z50520514)
http://linked.open...iv/cisloPeriodika
  • 3
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
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http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 97081
http://linked.open...ai/riv/idVysledku
  • RIV/68378050:_____/13:00390945
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • coiled coil; polymer therapeutics; scFv (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [0E41A62295F4]
http://linked.open...i/riv/nazevZdroje
  • Biomacromolecules
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 14
http://linked.open...iv/tvurceVysledku
  • Fábry, Milan
  • Král, Vlastimil
  • Kovář, Marek
  • Laga, Richard
  • Pechar, Michal
  • Pola, Robert
  • Sieglová, Irena
  • Ulbrich, Karel
  • Kabešová, Martina
http://linked.open...ain/vavai/riv/wos
  • 000316044700034
http://linked.open...n/vavai/riv/zamer
issn
  • 1525-7797
number of pages
http://bibframe.org/vocab/doi
  • 10.1021/bm3019592
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