Lehner A F, Burzynski S R, Hendry L B
Drugs Exp Clin Res. 1986;12 Suppl 1:57-72.
Antineoplaston A10 (3-phenylacetylamino-2,6-piperidinedione), a peptide analogue originally isolated from human urine and serum, appears to have antineoplastic activity. In view of the close resemblance of the structure of A10 to that of DNA intercalative anticancer drugs, spectroscopic studies were performed to determine whether its mode of action could similarly involve binding to DNA. DNA thermal denaturation studies demonstrated that A10 was capable of interacting with DNA in a specific manner; of the synthetic polynucleotides employed in this study, A10 had the greatest effect on poly(dA-dG).poly(dC-dT), suggesting some sequence preference. However, ultraviolet and fluorescence spectroscopic studies demonstrated that interactions of A10 with DNA were weak in comparison to those of classical intercalating agents. Mass spectroscopic studies suggested that A10 did not react covalently with DNA. The weak yet apparently specific interaction of A10 with DNA indicates that the mode of action of A10 may involve binding to chromatin, facilitated by nuclear protein receptors analogous to steroid and thyroid hormones.
抗肿瘤素A10（3-苯乙酰氨基-2,6-哌啶二酮）是一种最初从人尿液和血清中分离出来的肽类似物，似乎具有抗肿瘤活性。鉴于A10的结构与DNA嵌入型抗癌药物的结构非常相似，因此进行了光谱研究，以确定其作用方式是否同样涉及与DNA结合。DNA热变性研究表明，A10能够以特定方式与DNA相互作用；在本研究中使用的合成多核苷酸中，A10对聚（dA-dG）·聚（dC-dT）的影响最大，表明存在一定的序列偏好。然而，紫外和荧光光谱研究表明，与经典嵌入剂相比，A10与DNA的相互作用较弱。质谱研究表明，A10不会与DNA发生共价反应。A10与DNA之间微弱但明显具有特异性的相互作用表明，A10的作用方式可能涉及与染色质结合，这是由类似于类固醇和甲状腺激素的核蛋白受体促进的。
