title: Chemical modification improves the stability of the DNA aptamer GBI-10 and its affinity towards tenascin-C.
abstract: Aptamers are useful tools in molecular imaging due to their numerous attractive properties, such as excellent affinity and selectivity to diverse types of target molecules and biocompatibility. We carried out structure-activity relationship studies with the tenascin-C (TN-C) binding aptamer GBI-10, which is a promising candidate in tumor imaging. To increase the tumor targeting ability and nuclease resistance under physiological conditions, systematic modifications of GBI-10 with single and multiple 2'-deoxyinosine (2'-dI) or d-/l-isonucleoside (d-/l-isoNA) were performed. Results indicated that sector 3 of the proposed secondary structure is the most important region for specific binding with TN-C. By correlating the affinity of eighty-four GBI-10 derivatives with their predicted secondary structure by Zuker Mfold, we first validated the preferred secondary structure at 37 °C. We found that d-/l-isoNA modified GBI-10 derivatives exhibited improved affinity to the target as well as plasma stability. Affinity measurement and confocal imaging analysis highlighted one potent compound: 4AL/26TL/32TL, which possessed a significantly increased targeting ability to tumor cells. These results revealed the types of modified nucleotides, and the position and number of substituents in GBI-10 that were critical to the TN-C binding ability. Stabilized TN-C-binding DNA aptamers were prepared and they could be further developed for tumor imaging. Our strategy to introduce 2'-dI and d-/l-isoNA modifications after the selection process is likely to be generally applicable to improve the in vivo stability of aptamers without compromising their binding ability.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. guanzhu_gz@bjmu.edu.cn yangzj@bjmu.edu.cn #likunfeng@bjmu.edu.cn #m15210549140@163.com star_jin@sohu.com hsinmengfan@163.com woxihuandahai@126.com shiyizhaoyi@126.com wuyun_sioc@hotmail.com zdszlh@bjmu.edu.cn.
authors.forename: Kunfeng
authors.initials: K
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. guanzhu_gz@bjmu.edu.cn yangzj@bjmu.edu.cn #likunfeng@bjmu.edu.cn #m15210549140@163.com star_jin@sohu.com hsinmengfan@163.com woxihuandahai@126.com shiyizhaoyi@126.com wuyun_sioc@hotmail.com zdszlh@bjmu.edu.cn.
authors.forename: Jiali
authors.initials: J
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. guanzhu_gz@bjmu.edu.cn yangzj@bjmu.edu.cn #likunfeng@bjmu.edu.cn #m15210549140@163.com star_jin@sohu.com hsinmengfan@163.com woxihuandahai@126.com shiyizhaoyi@126.com wuyun_sioc@hotmail.com zdszlh@bjmu.edu.cn.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. guanzhu_gz@bjmu.edu.cn yangzj@bjmu.edu.cn #likunfeng@bjmu.edu.cn #m15210549140@163.com star_jin@sohu.com hsinmengfan@163.com woxihuandahai@126.com shiyizhaoyi@126.com wuyun_sioc@hotmail.com zdszlh@bjmu.edu.cn.
authors.forename: Xiantao
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. guanzhu_gz@bjmu.edu.cn yangzj@bjmu.edu.cn #likunfeng@bjmu.edu.cn #m15210549140@163.com star_jin@sohu.com hsinmengfan@163.com woxihuandahai@126.com shiyizhaoyi@126.com wuyun_sioc@hotmail.com zdszlh@bjmu.edu.cn.
authors.forename: Xinmeng
authors.initials: X
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. guanzhu_gz@bjmu.edu.cn yangzj@bjmu.edu.cn #likunfeng@bjmu.edu.cn #m15210549140@163.com star_jin@sohu.com hsinmengfan@163.com woxihuandahai@126.com shiyizhaoyi@126.com wuyun_sioc@hotmail.com zdszlh@bjmu.edu.cn.
authors.forename: Liyu
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. guanzhu_gz@bjmu.edu.cn yangzj@bjmu.edu.cn #likunfeng@bjmu.edu.cn #m15210549140@163.com star_jin@sohu.com hsinmengfan@163.com woxihuandahai@126.com shiyizhaoyi@126.com wuyun_sioc@hotmail.com zdszlh@bjmu.edu.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. guanzhu_gz@bjmu.edu.cn yangzj@bjmu.edu.cn #likunfeng@bjmu.edu.cn #m15210549140@163.com star_jin@sohu.com hsinmengfan@163.com woxihuandahai@126.com shiyizhaoyi@126.com wuyun_sioc@hotmail.com zdszlh@bjmu.edu.cn.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Guan
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. guanzhu_gz@bjmu.edu.cn yangzj@bjmu.edu.cn #likunfeng@bjmu.edu.cn #m15210549140@163.com star_jin@sohu.com hsinmengfan@163.com woxihuandahai@126.com shiyizhaoyi@126.com wuyun_sioc@hotmail.com zdszlh@bjmu.edu.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. guanzhu_gz@bjmu.edu.cn yangzj@bjmu.edu.cn #likunfeng@bjmu.edu.cn #m15210549140@163.com star_jin@sohu.com hsinmengfan@163.com woxihuandahai@126.com shiyizhaoyi@126.com wuyun_sioc@hotmail.com zdszlh@bjmu.edu.cn.
authors.forename: Lihe
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. guanzhu_gz@bjmu.edu.cn yangzj@bjmu.edu.cn #likunfeng@bjmu.edu.cn #m15210549140@163.com star_jin@sohu.com hsinmengfan@163.com woxihuandahai@126.com shiyizhaoyi@126.com wuyun_sioc@hotmail.com zdszlh@bjmu.edu.cn.
authors.forename: Zhenjun
authors.identifier: http://orcid.org/0000-0001-7614-595X
authors.initials: Z
authors.lastname: Yang
mesh_terms: D016475:3T3 Cells; D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry; D002478:Cells, Cultured; D005453:Fluorescence; D005910:Glioma / Q000000981:diagnostic imaging*; D006801:Humans; D051379:Mice; D056004:Molecular Dynamics Simulation; D057054:Molecular Imaging; D019063:Tenascin / Q000737:chemistry*
chemical_list: D052157:Aptamers, Nucleotide; D019063:Tenascin