Bailly C, Waring M J
INSERM U-124 et Laboratoire de Pharmacologie Antitumorale du Centre Oscar Lambret, IRCL, Place de Verdun, 59045 Lille, France.
Nucleic Acids Res. 1998 Oct 1;26(19):4309-14. doi: 10.1093/nar/26.19.4309.
2,6-Diaminopurine (DAP) is an analogue of adenine which can be converted to nucleotides that serve as substrates for incorporation into nucleic acids by polymerases in place of (d)AMP. It pairs with thymidine (or uracil), engaging in three hydrogen bonds of the Watson-Crick type. The result of DAP incorporation is to add considerable stability to the double helix and to impart other structural features, such as an altered groove width and disruption of the normal spine of hydration. DNA containing DAP may or may not be recognized by restriction endonucleases; RNA containing DAP may not engage in normal splicing. The DAP.T pair affects the local flexibility of DNA and impedes the interaction with helix bending proteins. By providing a non-canonical hydrogen bond donor in the minor groove and/or blocking access to the floor of that groove it strongly affects interactions with small molecules such as antibiotics and anticancer drugs. Examples which illustrate altered recognition of nucleotide sequences in DAP-containing DNA are presented: changed sites of cutting by bleomycin, photocleavage by uranyl nitrate and footprinting with mithramycin. Using DNA in which both A-->DAP and G-->Inosine substitutions have been made it is possible to assess precisely the role of the purine 2-amino group in ligand-DNA recognition.
2,6 -二氨基嘌呤（DAP）是腺嘌呤的类似物，它可以转化为核苷酸，作为底物被聚合酶掺入核酸中以取代（d）AMP。它与胸腺嘧啶（或尿嘧啶）配对，形成三个沃森-克里克型氢键。掺入DAP的结果是使双螺旋增加相当大的稳定性，并赋予其他结构特征，如改变的沟宽和破坏正常的水化骨架。含有DAP的DNA可能被或不被限制性内切酶识别；含有DAP的RNA可能无法进行正常剪接。DAP.T对影响DNA的局部柔韧性，并阻碍与螺旋弯曲蛋白的相互作用。通过在小沟中提供一个非经典氢键供体和/或阻止进入该沟的底部，它强烈影响与小分子如抗生素和抗癌药物的相互作用。给出了说明含DAP的DNA中核苷酸序列识别改变的例子：博来霉素切割位点的改变、硝酸铀酰光切割以及与光神霉素的足迹分析。使用同时进行了A→DAP和G→肌苷取代的DNA，可以精确评估嘌呤2 -氨基在配体-DNA识别中的作用。
