d-/l-Isothymidine incorporation in the core sequence of aptamer BC15 enhanced its binding affinity to the hnRNP A1 protein

文献情報

出版日 2018-09-19

DOI 10.1039/C8OB01454J

インパクトファクター 3.876

著者

Liyu Li, Kunfeng Li, Guangpu Zhang, Yuan Ma, Baobin Cai, Shaohua Li, Hongmei Ding, Jiali Deng, Xiyan Nan, Jing Sun, Yun Wu, Ningsheng Shao, Lihe Zhang, Zhenjun Yang

原文を見る

要旨

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.

掲載誌

Organic & Biomolecular Chemistry

CiteScore: 3.4

自己引用率: 10.3%

年間論文数: 1041

Organic & Biomolecular Chemistry (OBC) publishes original and high impact research and reviews in organic chemistry. We welcome research that shows new or significantly improved protocols or methodologies in total synthesis, synthetic methodology or physical and theoretical organic chemistry as well as research that shows a significant advance in the organic chemistry or molecular design aspects of chemical biology, catalysis, supramolecular and macromolecular chemistry, theoretical chemistry, mechanism-oriented physical organic chemistry, medicinal chemistry or natural products. Articles published in the journal should report new work which makes a highly-significant impact in the field. Routine and incremental work is generally not suitable for publication in the journal. More details about key areas of our scope are below. In all cases authors should include in their article clear rationale for why their research has been carried out.