Probing the Key Binding Sequence and Improvement of the Stability of a β‐Bungarotoxin‐binding Aptamer in Snake Venom

Bulletin of the Korean Chemical Society

Jing Yu¹  Qili Mi²  Xuemei Li²  Ying Zheng²  Jinglin Wang²  Jie Wang²  Quanshui Fan³  Fengping Ye⁴  Ning Zhang⁵  Zhongping Gao⁵ 

[1] Hospital of Unit 77256, PLA Kunming 650225 China;Institute of Military Medicine Chengdu Military Region's Center for Disease Control & Prevention Kunming 650032 China;Medical Department General Hospital of Qinghai Armed Police Xining 810000 China;State Key Laboratory of Pathogen and Biosecurity Institute of Microbiology and Epidemiology Beijing 100071 China;Technology Center China Tobacco Yunnan Industrial Co., Ltd Kunming 650231 China

关键词: Aptamer;    β;    ‐;    Bungarotoxin;    Biostability;    ;    Bungarus multicinctus ;    Chemical modification;   

DOI  :  10.1002/bkcs.10737

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

Chemical modifications of the nucleotides can improve the stability of aptamers against enzyme degradation in serum, but it is not clear whether these methods are effective in snake venom. In this study, a DNA aptamer, βB‐1, which specifically recognize β‐bungarotoxin and Bungarus multicinctus venom was chosen, and the key binding sequence of the aptamer was determined. Based on the secondary structure of the truncated aptamer, locked nucleic acids and 2′‐O‐methyl nucleotides were applied to modify the stem and loop sequences, respectively. In addition, a 3′‐3′‐thymidine cap was also adopted to block the 3′ end. It was shown that these chemical modifications can all enhance the stability of the aptamer in snake venom. Simultaneously, modified aptamer with the above modifications in one sequence exhibited a significantly elevated biostability, with the half‐life improved from several minutes to 210 min while maintaining its binding affinity to the target.

【 授权许可】

Unknown