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学科主题: 药学
题名:
Stability and bioactivity of thrombin binding aptamers modified with D-/L-isothymidine in the loop regions
作者: Cai, Baobin; Yang, Xiantao; Sun, Lidan; Fan, Xinmeng; Li, Liyu; Jin, Hongwei; Wu, Yun; Guan, Zhu; Zhang, Liangren; Zhang, Lihe; Yang, Zhenjun
刊名: ORGANIC & BIOMOLECULAR CHEMISTRY
发表日期: 2014
DOI: 10.1039/c4ob01525h
卷: 12, 期:44, 页:8866-8876
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Organic
研究领域[WOS]: Chemistry
关键词[WOS]: G-QUADRUPLEX ; DNA APTAMER ; BIOLOGICAL-PROPERTIES ; MOLECULAR-MECHANICS ; ACYCLIC NUCLEOTIDE ; SILENCING ACTIVITY ; CONTINUUM MODELS ; NUCLEIC-ACID ; OLIGONUCLEOTIDES ; D(GGTTGGTGTGGTTGG)
英文摘要:

Thrombin binding aptamer (TBA) is a 15-mer single-strand DNA that was identified by SELEX screening technology. It adopts a chair-type antiparallel G-quadruplex and can specifically interact with thrombin, thus inhibiting blood coagulation. Isonucleoside (isoNA) is a type of nucleoside isomer in which the base is shifted to 2′-positions of the glycosyl group, endowed with the ability to modulate local conformation of nucleotides, and L-isoNA could alter the conformation more due to the inversion of glycosyl configuration. Incorporation of L-isothymidine (L-isoT) at T3, T9, T12 positions and D-isoT at the T7 position in TBA′s loop regions promoted the formation of G-quadruplex, resulting in enhanced affinity with thrombin and an increased anticoagulant effect. Computer simulation indicated that TBA-12L showed the strongest binding with thrombin, which was consistent with experimental results. The bioactivity of double isoNA incorporated TBA with D-IsoT at T7 and L-IsoT at T12 was comparable to that of TBA-12L, suggesting that the T12 of TBA was very important in interaction with thrombin. Our study also suggested that TBA might interact with two thrombin molecules through the TT loops (T3T4, T12T13) and TGT loop, but the second bonding did not show additional biological effects.

语种: 英语
所属项目编号: 2012CB720604 ; 2012AA022501 ; 21332010 ; 20932001
项目资助者: Ministry of Science and Technology of China ; National Natural Science Foundation of China
WOS记录号: WOS:000344236200011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62464
Appears in Collections:北京大学药学院_期刊论文

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作者单位: Peking Univ, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

Recommended Citation:
Cai, Baobin,Yang, Xiantao,Sun, Lidan,et al. Stability and bioactivity of thrombin binding aptamers modified with D-/L-isothymidine in the loop regions[J]. ORGANIC & BIOMOLECULAR CHEMISTRY,2014,12(44):8866-8876.
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