D-/L-Isothymidine incorporation in the core sequence of aptamer BC15 enhanced its binding affinity to the hnRNP A1 protein,Organic & Biomolecular Chemistry

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D-/L-Isothymidine incorporation in the core sequence of aptamer BC15 enhanced its binding affinity to the hnRNP A1 protein
Organic & Biomolecular Chemistry ( IF 2.9 ) Pub Date : 2018-09-19 , DOI: 10.1039/c8ob01454j
Liyu Li _{1,

2,

3,

4,

5} , Xiantao Yang _{1,

2,

3,

4,

5} , Kunfeng Li _{1,

2,

3,

4,

5} , Guangpu Zhang _{1,

2,

3,

4,

5} , Yuan Ma _{1,

2,

3,

4,

5} , Baobin Cai _{1,

2,

3,

4,

5} , Shaohua Li _{5,

6,

7,

8} , Hongmei Ding _{5,

6,

7,

8} , Jiali Deng _{1,

2,

3,

4,

5} , Xiyan Nan _{1,

2,

3,

4,

5} , Jing Sun _{1,

2,

3,

4,

5} , Yun Wu _{1,

2,

3,

4,

5} , Ningsheng Shao _{5,

6,

7,

8} , Lihe Zhang _{1,

2,

3,

4,

5} , Zhenjun Yang _{1,

2,

3,

4,

5}

Affiliation

The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was reported to participate in the development of a variety of tumors. BC15 is a DNA aptamer targeting hnRNP A1. Firstly, through sequence truncation, we identified 31-mer sequence BC15–31 as the core sequence of BC15 with a strong binding affinity and high selectivity to the hnRNP A1 protein. Isothymidine (isoT) modification was then applied for the structural optimization of BC15–31, systematic modification and biological evaluation were carried out. Incorporation of isoT in the 1,3 sites at the 5′-end of BC15–31 can significantly enhance the protein affinity. Chemical modifications close to the 3′-end can greatly improve the stability of the aptamer. Furthermore, BC15–31 modified with isoT at both the 5′-end and 3′-end displayed an additive effect with enhanced bioactivity and stability at the same time. Our study strategy on BC15 provides a useful guideline for chemical modification and optimization of the aptamer for further clinical application.

中文翻译：

D- / L-异胸苷掺入适体BC15的核心序列中增强了其与hnRNP A1蛋白的结合亲和力

据报道，异质核糖核蛋白A1（hnRNP A1）参与了多种肿瘤的发展。BC15是靶向hnRNP A1的DNA适体。首先，通过序列截断，我们确定了31-mer序列BC15–31是BC15的核心序列，对hnRNP A1蛋白具有很强的结合亲和力和高选择性。然后将异胸苷（isoT）修饰用于BC15–31的结构优化，进行了系统修饰和生物学评估。在BC15–31的5'末端的1,3位点加入了isoT可以显着增强蛋白质的亲和力。接近3'端的化学修饰可以大大提高适体的稳定性。此外，在5'端和3'端均用isoT修饰的BC15–31表现出累加效应，同时具有增强的生物活性和稳定性。我们在BC15上的研究策略为适体的化学修饰和优化提供了有用的指导，可用于进一步的临床应用。

更新日期：2018-10-18

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