About: Polymer therapeutics with a coiled coil motif targeted against murine BCL1 leukemia

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An Entity of Type : http://linked.opendata.cz/ontology/domain/vavai/Vysledek, within Data Space : linked.opendata.cz associated with source document(s)

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	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	Ústav molekulární genetiky AV ČR, v. v. i.
http://linked.open...avai/riv/aktivita	I P Z
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	2014
http://linked.open...aciTvurceVysledku	Král, Vlastimil Fábry, Milan Sieglová, Irena
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Ústav molekulární genetiky AV ČR, v. v. i.
http://linked.open...dnocenehoVysledku	97081
http://linked.open...ai/riv/idVysledku	RIV/68378050:_____/13:00390945
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	coiled coil; polymer therapeutics; scFv (en)
http://linked.open.../riv/klicoveSlovo	coiled coil polymer therapeutics scFv
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	EB
http://linked.open...ichTvurcuVysledku	3 (xsd:int)
http://linked.open...cetTvurcuVysledku	9 (xsd:int)
http://linked.open...vavai/riv/projekt	Depletion of T regulatory cells without need of anti-CD25 mAb for effective chemoimmunotherapy by HPMA-based polymeric drugs and IL-2 immunocomplexes Multifunctional Polymer Systems with Cytostatic and Immunomobilizing Activities
http://linked.open...UplatneniVysledku	2013
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	Molekulárně genetické a buněčné základy klíčových biologických procesů: genová exprese, onkogeneze, replikace virů, imunita a vývoj organismů
issn	1525-7797
number of pages	9 (xsd:int)
http://bibframe.org/vocab/doi	10.1021/bm3019592

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