Helbecque N, Bernier J L, Hénichart J P
Biochem J. 1985 Feb 1;225(3):829-32. doi: 10.1042/bj2250829.
The synthesis of a new bifunctional compound in which two aminoacridine chromophores are linked by the bicyclic depsipeptidic backbone of des-N-tetramethylTriostin A is described. The molecule, bis-[(9-acridinyl)-D-seryl-L-alanyl-L-cysteinyl-L-valine] dilactone disulphide, structurally analogous to the antibiotic anti-tumour drug Triostin A, is shown to possess a high affinity to DNA and to act as a bis-intercalator on the basis of spectroscopic, viscosimetric and thermal-denaturation studies. This model constitutes the first attempt of a synergic association between a peptidic moiety that mimics a naturally occurring drug and aminoacridine, the two parts themselves each exhibiting a high affinity for the DNA target.
本文描述了一种新型双功能化合物的合成，其中两个氨基吖啶发色团通过去-N-四甲基曲奥菌素A的双环缩肽主链连接。该分子双-[(9-吖啶基)-D-丝氨酰-L-丙氨酰-L-半胱氨酰-L-缬氨酸]二内酯二硫化物，在结构上类似于抗生素抗肿瘤药物曲奥菌素A，基于光谱、粘度测定和热变性研究表明，它对DNA具有高亲和力，并作为双嵌入剂起作用。该模型首次尝试了模拟天然药物的肽部分与氨基吖啶之间的协同结合，这两部分本身对DNA靶点均表现出高亲和力。
