《結構修飾的siRNA合成和RNA干擾技術在藥物靶標尋找中的研究》是張禮和為項目負責人，北京大學為依託單位的重點項目。
基本介紹
- 中文名：結構修飾的siRNA合成和RNA干擾技術在藥物靶標尋找中的研究
- 項目類別 ：重點項目
- 依託單位 ：北京大學
- 項目負責人：張禮和
科研成果 ,項目摘要,
科研成果
序號 | 標題 | 類型 | 作者 |
|---|---|---|---|
1 | c-Met inhibitor SU11274 enhances the response of the prostate cancer cell line DU145 to ionizing radiation | 期刊論文 | Hongliang Yu|Xiaoying Li|Shaoqian Sun|Xianshu Gao|Demin Zhou| |
2 | Elucidation of the pharmacophore of echinocystic acid as a new lead for blocking HCV entry. | 期刊論文 | De-Min Zhou|Qi Wang|Su-Long Xiao|Fei Yu|Min Ye|Yong-Xiang Zheng|Chuan-Ke Zhao|Di-An Sun|Li-He Zhang| |
3 | Synthesis, physicochemical, biological properties of oligonucleotides incorporated with amino-isonucleosides | 期刊論文 | Fang Wang|Yue Chen|Ye Huang|Hong-Wei Jin|Liang-Ren Zhang|Zhen-Jun Yang|Li-He Zhang| |
4 | Synthesis and biological evaluation of peptide-siRNA conjugates with phosphodiester unit as linker | 期刊論文 | Xiaofeng Wang|Ye Huang|Yang Liu|Yue Chen|Hongwei Jin|Yi Zheng|Quan Du|Zhenjun Yang|Lihe Zhang| |
5 | Facile preparation of two tetrols from permethylated α-cyclodextrin and unambiguous NMR analysis | 期刊論文 | Sulong Xiao|Demin Zhou|Ming Yang|Pierre Sinaÿ|Matthieu Sollogoub|Yongmin Zhang| |
6 | Strand antagonism in RNAi: an explanation of differences in potency between intracellularly expressed siRNA and shRNA | 期刊論文 | Demin Zhou|Tingting Sun|Chuanke Zhao|Yongxiang Zheng|Yufan Zhang|Weijing Cai|Qiuchen He|Kaz Taira|Lihe Zhang| |
7 | Loss of silencing activity caused by 5’-terminal modification with D-/L-isonucleotide (isoNA) or locked nucleic acid (LNA) could not be restored by 5’-terminal phosphorylation | 期刊論文 | Ye Huang|Zhuo Chen|Zhuo Huang|Yating Li|Yue Chen|Zhenjun Yang|Lihe Zhang| |
8 | Long double-stranded multiplex siRNAs for dual genes silencing | 期刊論文 | Peng, Wei|Jianxin Chen|Yinchao Qin|Zhenjun Yang|York Yuanyuan Zhu| |
9 | Chemically modified siRNAs and their conjugates | 期刊論文 | Yue Chen|Xiao-Feng Wang|Ye Huang|Li-He Zhang|Zhen-Jun Yang| |
10 | Development of Oleanane-Type Triterpenes as a New Class of HCV Entry Inhibitors | 期刊論文 | Demin Zhou|Qi Wang|Zhen Zhang|Yiyun Peng|Yunyan Qiu|Yongying Shi|Yongxiang Zheng|Sulong Xiao|Han Wang| |
11 | Conjugation of cyclodextrin with fullerene as a new class of HCV entry inhibitors | 期刊論文 | De-min Zhou|Qi Wang|Fei Yu|Yi-yun Peng|Ming Yang|Matthieu Sollogoub|Pierre Sinaÿ|Yong-min Zhang|Li-he Zhang| |
12 | The Effects of conformational alteration induced by D-/L-isonucleoside incorporation in siRNA on their stability in serum and silencing activity | 期刊論文 | Ye Huang|Zhuo Chen|Yue Chen|Hao Zhang|Yichao Zhang|Yilei Zhao|Zhenjun Yang|Lihe Zhang| |
13 | BODIPY-based sulfoxide: Synthesis, photophysical characterization and response to benzenethiols | 期刊論文 | Chunchang Zhao|Xuzhe Wang|Jian Cao|Peng Feng|Jinxin Zhang|Yanfen Zhang|Yang Yang|Zhenjun Yang| |
14 | 干擾RNA(siRNA)藥物研究進展 | 學術專著 | 陳玥|黃野|楊振軍| |
15 | Synthesis and properties of a novel L-isonucleosides modified oligonucleotides and siRNAs | 期刊論文 | Jun Zhang|Yue Chen|Ye Huang|Hong-Wei Jin|Ren-Ping Qiao|Lei Xing|Liang-Ren Zhang|Zhen-Jun Yang|Li-He Zhang| |
16 | Medicinal Chemistry of Nucleic Acids | 學術專著 | Li-He Zhang|Zhen Xi|Jyoti Chattopadhyaya|Sidney M. Hecht| |
17 | Thymidine based amphiphiles and their bonding to DNA | 期刊論文 | Delin Pan,|Chen Tang|Xinmeng Fan|Yating Li|Xiantao Yang|Hongwei Jin|Zhu Guan|Zhenjun Yang|Lihe Zhang| |
18 | A solid-phase method for peptide-siRNA conjugates based on Click Chemistry | 期刊論文 | Yang Liu|Xiao-Feng Wang|Yue Chen|Li-He Zhang|Zhen-Jun Yang| |
19 | Solid phase synthesis of peptide-siRNA conjugates containing disulfide bond unit | 期刊論文 | Xiao-Feng Wang|Xian-Tao Yang|Yue Chen|Yang Liu|Lang Zou|Zhen-Jun Yang|Li-He Zhang| |
20 | Development of a high-content screening method to evaluate the cellular population-based biological actvity of new siRNA delivering reagent | 期刊論文 | Yating Li|Yi Zheng|Delin Pan|Bo Xu|Yun Wu|Zhenjun Yang|Lihe Zhang| |
21 | Modification of oligonucleotides by isonucleosides incorporation and peptides conjugation | 期刊論文 | Ye Huang|Xiaofeng Wang|Zhenjun Yang|Lihe Zhang| |
22 | Synthesis of four mono- functionalized α-cyclodextrin derivatives for further confirming DIBAL-H-promoted bis-de-O-methylation mechanism | 期刊論文 | Sulong Xiao|Ming Yang|Fei Yu|Lihe Zhang|Demin Zhou|Pierre Sinay|Yongmin Zhang| |
項目摘要
siRNA作為治療劑呈現了很好的前景，主要問題表現為：(1)體內轉運困難，合成的siRNA導入細胞後易被RNase降解, 難於準確地到達靶部位; (2)RNA干擾技術能夠特異有效地指導基因沉默, 但在某些情況下存在脫靶效應(Off-Target Effect), 即非特異性抑制作用;(3)如何方便經濟地設計和製備特定的siRNA文庫，以便利用RNAi技術尋找藥物靶和有治療作用的siRNA。本項申請計畫開展：a. 化學修飾的siRNA，包括帶有氨基及其它基團的異核苷並用於摻入siRNA，及設計合成脂類、肽類等綴合的siRNA; b. 提高修飾的siRNA的RNAi效應、細胞膜通透性和酶穩定性；c. 通過siRNA對基因沉黙機制的研究找到脫靶效應的原因、規律, 提高與靶mRNA作用選擇性，從而設計合成作用專一的siRNA；d.利用前期建立的siRNA文庫和篩選方法用於藥靶尋找。
