D-/l-Isothymidine incorporation in the core sequence of aptamer BC15 enhanced its binding affinity to the hnRNP A1 protein. Issue 40 (1st October 2018)

• Record Type: Journal Article
• Authors: Li, Liyu; Yang, Xiantao; Li, Kunfeng; Zhang, Guangpu; Ma, Yuan; Cai, Baobin; Li, Shaohua; Ding, Hongmei; Deng, Jiali; Nan, Xiyan; Sun, Jing; Wu, Yun; Shao, Ningsheng; Zhang, Lihe; Yang, Zhenjun
• Is Part Of: Organic & biomolecular chemistry. Volume 16:Issue 40(2018)
• Page Start: 7488
• Page End: 7497
• Publication Date: 2018-10-01
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c8ob01454j
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Truncation ofBC15 andd -/l -isothymidine modification of its core sequence greatly enhanced the binding affinity and selectivity to the hnRNP A1 protein. Abstract : 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 sequenceBC15–31 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 ofisoT in the 1, 3 sites at the 5′-end ofBC15–31 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 withisoT at both the 5′-end and 3′-end displayed an additive effect with enhanced bioactivity and stability at the same time. Our study strategy onBC15 provides a useful guideline for chemical modification and optimization of the aptamer for further clinical application.