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.
Szabó
Rita
R
Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös L. University, Budapest 112, Hungary.
Bánóczi
Zoltán
Z
Mezo
Gábor
G
Láng
Orsolya
O
Kohidai
László
L
Hudecz
Ferenc
F
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000494:pharmacology*; D003630:Daunorubicin / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D057846:Cell-Penetrating Peptides; D003630:Daunorubicin