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Daunomycin-polypeptide conjugates with antitumor activity.


We have developed a group of water-soluble drug conjugates in which daunomycin (Dau) is coupled to cationic, amphoteric or anionic branched polypeptides and a new conjugate containing a cationic polypeptide carrier modified with a cell penetrating octaarginine. We investigated in vitro physiological activity of these conjugates in several aspects: in vitro cytotoxicity and cytostatic effect, adhesion and cellular uptake were examined on murine (J774 and L1210) and human (MonoMac6 and HL-60) leukemia cell lines and on murine bone marrow derived macrophages. We found that these processes are dependent on the properties of the carrier, on experimental conditions like concentration and incubation time. We found that attachment of polypeptide and cell penetrating peptide to the bioactive agent, depending on the cell line, could significantly improve the antitumor activity of the drug. Copyright © 2010 Elsevier B.V. All rights reserved.

Authors: Szabó R, Bánóczi Z, Mező G, Láng O, Kőhidai L, Hudecz F.
Journal: Biochim Biophys Acta. 1798(12):2209-2216
Year: 2010
PubMed: Find in PubMed