Supino R, Gibelli N, Zunino F
J Natl Cancer Inst. 1986 Aug;77(2):453-7.
The ability of the synthetic cationic polypeptide poly-L-lysine (PLL) to induce differentiation of Friend murine erythroleukemia cells was examined with the use of polymers of different molecular weights. Like other membrane-interacting agents (polar solvents), all the polymers tested were effective in inducing cell differentiation. This effect was found to be molecular weight dependent, as already reported for other membrane-related actions of these polymers. Since anthracyclines also exert direct effects on the cell membrane, the activity of the daunorubicin-PLL conjugate was also examined. The covalent linking of the drug to the polyamino acid somewhat reduced the differentiation-inducing activity in this system. Indeed, free daunorubicin was found to inhibit the maturational process. Although the inducing effect was observed when the free PLL or daunorubicin-linked PLL was added alone, polymers enhanced differentiation produced by suboptimal concentrations of dimethyl sulfoxide (DMSO). Since PLL was inactive as an initiator of the maturation of a DMSO-resistant line, it is likely that some events (presumably membrane-related effects) involved in the multistep stimulation process are common to polar-planar solvents and the polycationic polymer.
利用不同分子量的聚合物，研究了合成阳离子多肽聚-L-赖氨酸（PLL）诱导弗氏小鼠红白血病细胞分化的能力。与其他膜相互作用剂（极性溶剂）一样，所有测试的聚合物在诱导细胞分化方面均有效。正如已报道的这些聚合物的其他与膜相关的作用一样，发现这种作用依赖于分子量。由于蒽环类药物也对细胞膜有直接作用，因此还研究了柔红霉素-PLL缀合物的活性。药物与聚氨基酸的共价连接在该系统中 somewhat 降低了诱导分化的活性。事实上，发现游离柔红霉素会抑制成熟过程。尽管单独添加游离PLL或柔红霉素连接的PLL时观察到了诱导作用，但聚合物增强了次优浓度二甲基亚砜（DMSO）产生的分化。由于PLL作为DMSO抗性系成熟的引发剂无活性，因此多步刺激过程中涉及的一些事件（可能是与膜相关的作用）可能是极性平面溶剂和聚阳离子聚合物所共有的。
