基于菁染料骨架的G-四链体DNA识别探针的研究进展

doi:10.6023/cjoc202203025

摘要/Abstract

富含鸟嘌呤(G)的DNA序列可形成一种特殊的核酸二级结构, 称为G-四链体DNA, 其广泛地分布于真核生物基因组, 与癌症的形成和发展关系密切. 以G-四链体为靶点的小分子荧光探针的开发, 对于研究G-四链体在生物体内的生物学功能及靶向抗癌药物具有重要的意义. 菁染料是一种应用广泛的生物标记用荧光染料, 具有修饰位点多及光谱范围可调等优点, 骨架内的刚性结构部分可通过π-π堆积、疏水作用等非共价键作用结合到G-四链体的末端或沟槽中, 诱导菁染料产生不同的光谱信号变化进而实现对G-四链体的选择性识别, 近年来成为G-四链体识别探针领域研究的热点. 综述了以菁染料为骨架的G-四链体DNA识别探针的研究进展, 并简要介绍了该类探针分子的分子设计和性能, 对探针与G-四链体DNA的亲和性和选择性等方面进行了评述, 最后展望了该类G-四链体识别探针的研究和发展方向.

关键词: 菁染料, G-四链体DNA, 识别探针, 分子设计

Guanine-rich (G) DNA sequences can form a special nucleic acid secondary structure called G-quadruplex DNA, which is widely distributed in eukaryotic genomes and is closely associated with the formation and development of cancer. The development of small molecule fluorescent probes targeting G-quadruplexes is of great significance for the study of the biological functions of G-quadruplexes in organisms and for targeting anti-cancer drugs. The cyanine dyes are widely used as fluorescent dyes for biolabelling, with the advantages of multiple modification sites and adjustable spectral range. The rigid structural part of the backbone can be bound to the end of the G-quadruplex or groove through π-π stacking, hydrophobic interaction and other non-covalent bonding, inducing different spectral signal changes of cyanine dyes to achieve selective recognition of the G-quadruplex. This has become a hot topic of research in the field of G-quadruplex recognition in recent years. Herein, the research progresses in the field of G‑quadruplex recognition probes based on cyanine dye are reviewed. Molecular design and propertis of this kind of probes are briefly introduced, and the affinity and selectivity of probes for G-quadruplex DNA are also commented. Moreover, the future trends of cyanine-based recognition probes for G‑quadruplex are briefly introduced.

Key words: cyanine dye, G-quadruplex DNA, recognition probe, molecular design

引用此文

关丽, 毛永爆, 周艳艳, 冯潇雯, 付义乐. 基于菁染料骨架的G-四链体DNA识别探针的研究进展[J]. 有机化学, 2022, 42(8): 2406-2417.

Li Guan, Yongbao Mao, Yanyan Zhou, Xiaowen Feng, Yile Fu. Research Progress in Cyanine-Based Recognition Probes for G-Quadruplex DNA[J]. Chinese Journal of Organic Chemistry, 2022, 42(8): 2406-2417.

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G4探针	λ_max/λ_em^a/nm	结合/解离常数^b	选择性	识别方法	靶向细胞器
2	≈520/≈550	—	G4s	荧光^c	—
3	527/584	0.25×10⁶ L•mol^–1	G4s	荧光	细胞核
4c	552/585	1.12×10⁶ L•mol^–1	G4s	荧光	细胞核
5	516/613	—	G4s	比色^d, 荧光	细胞质、核(主要)
6a	473/630	0.965×10⁶ L•mol^–1	G4s	荧光	细胞核仁
6b	425/≈550	6 μmol•L^–1	混合型端粒G4s	比色, 荧光	细胞核为主
6f	/650	—	G4s	荧光	线粒体
6g	/530	—	G4s	荧光	线粒体
6h	448/≈650	1.5~10.5 μmol•L^–1	G4s	荧光	线粒体
6i	525/630	0.69~11.8 μmol•L^–1	选择性较差	荧光	细胞核
6j	561/694	(0.319~0.929)×10⁶ L•mol^–1	反平行端粒G4s	荧光	线粒体
7	535/	0.429~0.735 μmol•L^–1	G4s	比色	—
8	515/588	2.00~2.35 μmol•L^–1	平行G4s	荧光	—
14	646/680	0.48×10⁶ L•mol^–1	平行MYC G4s	荧光	—
15	599/651	(11.2~39.7)×10⁶ L•mol^–1	G4s	荧光	—
17	499/650	2.08×10⁶ L•mol^–1	端粒G4s	荧光	细胞核仁
18	440/480	—	G4s	荧光	溶酶体
22	607/602	—	分子内平行和混合G4s	比色, 荧光	—
23	480/530	—	平行MYC G4s	荧光	—
25	450/604	(0.12~0.65)×10⁶ L•mol^–1	平行MYC G4s	比色, 荧光	—
26	553/	—	椅式反平行G4s	CD	—
27a	577/715	0.82×10⁶ L•mol^–1	G4s	荧光	—
27b	630/700	(0.18~2)×10⁶ L•mol^–1	G4s	比色	—
27c	626/	9.3×10⁶ L•mol^–1	G4s	荧光	—
28	516/550	(0.13~3.16) μmol•L^–1	G4s	荧光	—
30	613/710	(8.93~19.7) μmol•L^–1	平行G4s	比色, 荧光	—
31	620, 800/700	k₁: (0.12~0.9)×10⁶ L•mol^–1 k₂: (0.036~0.27)×10⁶ L•mol^–1	平行G4s	比色, 荧光	—

G4探针	λ_max/λ_em^a/nm	结合/解离常数^b	选择性	识别方法	靶向细胞器
2	≈520/≈550	—	G4s	荧光^c	—
3	527/584	0.25×10⁶ L•mol^–1	G4s	荧光	细胞核
4c	552/585	1.12×10⁶ L•mol^–1	G4s	荧光	细胞核
5	516/613	—	G4s	比色^d, 荧光	细胞质、核(主要)
6a	473/630	0.965×10⁶ L•mol^–1	G4s	荧光	细胞核仁
6b	425/≈550	6 μmol•L^–1	混合型端粒G4s	比色, 荧光	细胞核为主
6f	/650	—	G4s	荧光	线粒体
6g	/530	—	G4s	荧光	线粒体
6h	448/≈650	1.5~10.5 μmol•L^–1	G4s	荧光	线粒体
6i	525/630	0.69~11.8 μmol•L^–1	选择性较差	荧光	细胞核
6j	561/694	(0.319~0.929)×10⁶ L•mol^–1	反平行端粒G4s	荧光	线粒体
7	535/	0.429~0.735 μmol•L^–1	G4s	比色	—
8	515/588	2.00~2.35 μmol•L^–1	平行G4s	荧光	—
14	646/680	0.48×10⁶ L•mol^–1	平行MYC G4s	荧光	—
15	599/651	(11.2~39.7)×10⁶ L•mol^–1	G4s	荧光	—
17	499/650	2.08×10⁶ L•mol^–1	端粒G4s	荧光	细胞核仁
18	440/480	—	G4s	荧光	溶酶体
22	607/602	—	分子内平行和混合G4s	比色, 荧光	—
23	480/530	—	平行MYC G4s	荧光	—
25	450/604	(0.12~0.65)×10⁶ L•mol^–1	平行MYC G4s	比色, 荧光	—
26	553/	—	椅式反平行G4s	CD	—
27a	577/715	0.82×10⁶ L•mol^–1	G4s	荧光	—
27b	630/700	(0.18~2)×10⁶ L•mol^–1	G4s	比色	—
27c	626/	9.3×10⁶ L•mol^–1	G4s	荧光	—
28	516/550	(0.13~3.16) μmol•L^–1	G4s	荧光	—
30	613/710	(8.93~19.7) μmol•L^–1	平行G4s	比色, 荧光	—
31	620, 800/700	k₁: (0.12~0.9)×10⁶ L•mol^–1 k₂: (0.036~0.27)×10⁶ L•mol^–1	平行G4s	比色, 荧光	—