Szabó Rita, Bánóczi Zoltán, Mezo Gábor, Láng Orsolya, Kohidai László, Hudecz Ferenc
Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös L. University, Budapest 112, Hungary.
Biochim Biophys Acta. 2010 Dec;1798(12):2209-16. doi: 10.1016/j.bbamem.2010.07.023. Epub 2010 Jul 24.
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.
我们研发了一组水溶性药物偶联物，其中柔红霉素（Dau）与阳离子、两性离子或阴离子支链多肽偶联，以及一种含有经细胞穿透性八聚精氨酸修饰的阳离子多肽载体的新型偶联物。我们从几个方面研究了这些偶联物的体外生理活性：在小鼠（J774和L1210）和人（MonoMac6和HL-60）白血病细胞系以及小鼠骨髓来源的巨噬细胞上检测了体外细胞毒性和细胞生长抑制作用、黏附及细胞摄取情况。我们发现这些过程取决于载体的性质以及诸如浓度和孵育时间等实验条件。我们还发现，根据细胞系的不同，多肽和细胞穿透肽与生物活性剂的连接可显著提高药物的抗肿瘤活性。
