DNA with Purine–Purine Base Pairs: Size and Position of Isoguanine and 8-Aza-7-deazaisoguanine Clickable Residues Control the Molecular Recognition of Guanine and 5-Aza-7-deazaguanine,The Journal of Organic Chemistry

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DNA with Purine–Purine Base Pairs: Size and Position of Isoguanine and 8-Aza-7-deazaisoguanine Clickable Residues Control the Molecular Recognition of Guanine and 5-Aza-7-deazaguanine
The Journal of Organic Chemistry ( IF 3.3 ) Pub Date : 2022-08-10 , DOI: 10.1021/acs.joc.2c00812
Dasharath Kondhare ₁ , Aigui Zhang ₁ , Peter Leonard ₁ , Frank Seela _{1,

2}

Affiliation

Purine–purine base pairs represent an alternative recognition system to the purine-pyrimidine pairing reported by Watson and Crick. Modified purines are the source for non-canonical interactions. To mimic dG–dC interactions, 2′-deoxyisoguanosine (1a) and 8-aza-7-deaza-2′-deoxyisoguanosine (2a) are used to construct base pairs with 2′-deoxyguanosine or 5-aza-7-deaza-2′-deoxyguanosine (dZ). This work reports the chemical functionalization of 1a and its shape mimic 2a in purine–purine base pairs. Clickable rigid ethynyl and more flexible octadiynyl side chain derivatives of 1a and 2a were synthesized. They were protected and converted into phosphoramidites. Building blocks were employed in the synthesis of base-modified 12-mer oligonucleotides with clickable side chains. Pyrene azide was clicked to the linkers. After hybridization, oligonucleotides with purine–purine base pairs were constructed with linkers and pyrene adducts at position-8 of isoguanine and at position-7 of 8-aza-7-deazaisoguanine. Recognition and stability of purine–purine base pairs were explored using T_m values, thermodynamic data, and CD-spectroscopic changes. Side chains at position-7 of 8-aza-7-deazaisoguanine–guanine base pairs or with 5-aza-7-deazaguanine are well accommodated in DNA, whereas functionalization at 8-position of isoguanine makes the DNA unstable. Pyrene click adducts verified the observation. In conclusion, position-7 is the place of choice for purine–purine base pair functionalization.

中文翻译：

具有嘌呤-嘌呤碱基对的 DNA：异鸟嘌呤和 8-Aza-7-deaza-isoguanine 可点击残基的大小和位置控制鸟嘌呤和 5-Aza-7-deazaguanine 的分子识别

嘌呤 - 嘌呤碱基对代表了 Watson 和 Crick 报道的嘌呤 - 嘧啶配对的替代识别系统。修饰的嘌呤是非典型相互作用的来源。为了模拟 dG-dC 相互作用，使用 2'-deoxyisoguanosine ( 1a ) 和 8-aza-7-deaza-2'-deoxyisoguanosine ( 2a ) 与 2'-deoxyguanosine 或 5-aza-7-deaza- 构建碱基对2'-脱氧鸟苷 (dZ)。这项工作报告了嘌呤-嘌呤碱基对中1a的化学功能化及其形状模拟2a 。1a和2a的可点击刚性乙炔基和更灵活的辛二炔基侧链衍生物被合成了。它们受到保护并转化为亚磷酰胺。构建块用于合成具有可点击侧链的碱基修饰的 12 聚体寡核苷酸。芘叠氮化物被点击到接头。杂交后，在异鸟嘌呤的第 8 位和 8-aza-7-deazaisoguanine 的第 7 位用接头和芘加合物构建具有嘌呤-嘌呤碱基对的寡核苷酸。使用T _m探索了嘌呤-嘌呤碱基对的识别和稳定性值、热力学数据和 CD 光谱变化。8-aza-7-deazaisoguanine-guanine 碱基对或 5-aza-7-deazaguanine 的 7 位侧链很好地适应 DNA，而异鸟嘌呤 8 位的功能化使 DNA 不稳定。芘点击加合物验证了观察结果。总之，位置 7 是嘌呤-嘌呤碱基对功能化的首选位置。

更新日期：2022-08-10

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