INTERACTION OF AMINOACRIDINES WITH NUCLEIC ACIDS
INTERACTION OF AMINOACRIDINES WITH NUCLEIC ACIDS
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DOI：
10.1002/bip.1968.360060902
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发表时间：
1968-01-01
期刊：
影响因子：
2.9
通讯作者：
PEACOCKE, AR
中科院分区：
文献类型：
--
作者：
BLAKE, A;PEACOCKE, AR
氨基吖啶及其衍生物与核酸相互作用的性质继续引起采用许多不同技术的研究人员的关注。由于各种原因，这种兴趣持续存在。首先，氨基吖啶本身就是重要的抗菌剂和诱变剂。它们的抗菌作用长期以来一直是深入研究的主题1+，但在过去的六年里，它们诱导突变的能力，显然是通过在DKA中引起单核苷酸的缺失或插入，这已经达到了极限。通过溶菌酶的氨基酸序列测定，溶菌酶的氨基酸序列测定令人信服地证实了6，溶菌酶是由噬菌体T4中的丙黄素（3，G-二氨基吖啶）诱导的双突变改变的。这种与 DNA 相互作用的能力至少也是其抗菌活性的一部分，并且与它们对 DNA 引发的 DNA 和 RNA 聚合酶的抑制有关。 7* 8 然而，RNA 聚合酶的这种抑制似乎还涉及氨基吖啶对该酶的直接抑制，事实上，已知氨基吖啶会抑制许多酶，特别是那些参与氧化还原反应的酶。因此，氨基吖啶的抗菌活性可能取决于更广泛的作用，而不仅仅是它们与核酸的相互作用。其次，氨基吖啶由于其阳离子电荷和三个扁平芳环，其结构特征与其他与DNA相互作用引起极大兴趣的化合物相似，例如致癌物（多环烃和苯扎吖啶）；某些抗生素；核酸衍生物（嘌呤、核苷）；组织学染料，例如具有三个扁平稠合环的那些，例如派洛宁、甲苯胺蓝。以及甲基绿等三苯甲烷染料；菲啶杀锥虫剂，例如溴化乙锭；当然，还有其他吖啶衍生物。其中许多因其抗疟活性而闻名，例如atebrin。
The nature of the interaction of aminoacridines and their derivatives with nucleic acidst continues to engage the attention of investigators employing many different techniques. This interest persists for various reasons. First, the aminoacridines are themselves important antibacterial and mutagenic agents. Their antibacterial action has long been the subject of intensive study1+ but in the last six years it is their ability to induce mutations, apparently by causing deletion or insertion of a single nucleotide in DKA, which has been to the f~ re.~,~ This hypothesis has been convincingly confirmed6 by amino acid sequence determinations on lysozyme altered by a double mutation which was induced by proflavine (3, G-diaminoacridine) in bacteriophage T4. This ability to interact with DNA must also form part, at least, of the explanation of their antibacterial activity and has been associated with their inhibition of DNA-primed DNA and RNA polymerases. 7* 8 However, this inhibition of RNA polymerase nou-appearsg also to involve a direct inhibition of the enzyme by the aminoacridine, and, indeed, aminoacridines are known to inhibit a number of enzymes' notably those involved in oxidation-reduction reactions. So the antibacterial activity of aminoacridines is likely to depend on a wider range of effects than simply their interaction with the nucleic acids.Second, aminoacridines, on account both of their cationic charge and their three flat aromatic rings, have structural features similar to those of other compounds whose interaction with DNA is of great interest, such as carcinogens (both polycyclic hydrocarbons and benzacridines); certain antibiotics; nucleic acid derivatives (purines, nucleosides); histological dyes, eg, those with three flat, fused rings such as pyronin, toluidine blue. and triphenylmethane dyes such as methyl green; phenanthridine trypanocides, eg, ethidium bromide; and, of course, other acridine derivatives. many of which are noted for their antimalarial activity, eg, atebrin.