Polymer cancerostatics targeted with an antibody fragment bound via a coiled coil motif: in vivo therapeutic efficacy against murine BCL1 leukemia

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F18%3A00484884" target="_blank" >RIV/68378050:_____/18:00484884 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388971:_____/18:00484884 RIV/61389013:_____/18:00484884

Výsledek na webu

<a href="http://dx.doi.org/10.1002/mabi.201700173" target="_blank" >http://dx.doi.org/10.1002/mabi.201700173</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/mabi.201700173" target="_blank" >10.1002/mabi.201700173</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Polymer cancerostatics targeted with an antibody fragment bound via a coiled coil motif: in vivo therapeutic efficacy against murine BCL1 leukemia

Popis výsledku v původním jazyce

A BCL1 leukemia-cell-targeted polymer–drug conjugate with a narrow molecular weight distribution consisting of an N-(2-hydroxypropyl)methacrylamide copolymer carrier and the anticancer drug pirarubicin is prepared by controlled radical copolymerization followed by metal-free click chemistry. A targeting recombinant single chain antibody fragment (scFv) derived from a B1 monoclonal antibody is attached noncovalently to the polymer carrier via a coiled coil interaction between two complementary peptides. Two pairs of coiled coil forming peptides (abbreviated KEK/EKE and KSK/ESE) are used as linkers between the polymer-pirarubicin conjugate and the targeting protein. The targeted polymer conjugate with the coiled coil linker KSK/ESE exhibits 4× better cell binding activity and 2× higher cytotoxicity in vitro compared with the other conjugate. Treatment of mice with established BCL1 leukemia using the scFv-targeted polymer conjugate leads to a markedly prolonged survival time of the experimental animals compared with the treatment using the free drug and the nontargeted polymer-pirarubicin conjugate.

Název v anglickém jazyce

Polymer cancerostatics targeted with an antibody fragment bound via a coiled coil motif: in vivo therapeutic efficacy against murine BCL1 leukemia

Popis výsledku anglicky

A BCL1 leukemia-cell-targeted polymer–drug conjugate with a narrow molecular weight distribution consisting of an N-(2-hydroxypropyl)methacrylamide copolymer carrier and the anticancer drug pirarubicin is prepared by controlled radical copolymerization followed by metal-free click chemistry. A targeting recombinant single chain antibody fragment (scFv) derived from a B1 monoclonal antibody is attached noncovalently to the polymer carrier via a coiled coil interaction between two complementary peptides. Two pairs of coiled coil forming peptides (abbreviated KEK/EKE and KSK/ESE) are used as linkers between the polymer-pirarubicin conjugate and the targeting protein. The targeted polymer conjugate with the coiled coil linker KSK/ESE exhibits 4× better cell binding activity and 2× higher cytotoxicity in vitro compared with the other conjugate. Treatment of mice with established BCL1 leukemia using the scFv-targeted polymer conjugate leads to a markedly prolonged survival time of the experimental animals compared with the treatment using the free drug and the nontargeted polymer-pirarubicin conjugate.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10609 - Biochemical research methods

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Macromolecular Bioscience

ISSN

1616-5187

e-ISSN

—

Svazek periodika

18

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

11

Strana od-do

1-11

Kód UT WoS článku

000427446200008

EID výsledku v databázi Scopus

2-s2.0-85040669920