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AI与小分子药物中心
大健康研究院 副研究员
个人简介：
李志文，男，2020年毕业于北京协和医学院获博士学位；曾任职康龙化成、南京药石、安徽中科拓苒等公司从事抗肿瘤药物的设计合成以及创新药物、核苷酸、修饰核苷酸的工艺研发与生产。2024年8月入职大健康研究院先进医药与再生医学研究所汪燕翔课题组，致力于抗感染、抗肿瘤相关药物研究及转化。曾参与并发现一个治疗阴性耐药菌感染的新型单环beta-内酰胺抗生素候选物且实现转化，正进行IND申报。主要工作发表在Acta Pharm Sin B，Bioorg. Chem.、Org. Biomol. Chem.、Chem. Commun.等期刊，申请专利多篇。
研究兴趣及方向：
综合运用计算机辅助药物设计、传统药物化学理论等开发抗感染、抗肿瘤等药物候选物；设计合成用于疾病诊断和治疗的修饰核苷酸或核酸药物。
代表性工作：
1. Zhiwen Li?, Xi Lu?, Sheng Tang, Yinghong Li, Yanxiang Wang, Xiukun Wang, Zhihao Guo, Xinxin Hu, Tianyun Fan, Haigen Fu, Xuefu You, Danqing Song*. Synthesis, extensive structure-activity relationship and antibacterial evaluation of monobactams against resistant Gram-negative bacteria. Acta. Pharm. Sin. B. 2023, 137:3067-3079.
2. Xican Ma, Wei Guo, Xi Zhu, Zhiwen Li, Yinghong Li, Zhihao Guo, Yanxiang Wang, Jing Pang, Min Yuan, Zhenjun Li, Xuefu You, Xi Lu, Yishuang Liu, Danqing Song. Synthesis of peptidomimetics as antibiotic adjuvants for combination with aztreonam to combat MDR Pseudomonas aeruginosa. Eur J Med Chem. 2023, 260:115778.
3. Zhiwen Li ?, Xi Lu?, YanXiang Wang, XinXin Hu, LiMei Gao, HaiGen Fu, XueFu You, Sheng Tang, Dan–Qing Song. Synthesis and antibacterial evaluation against resistant Gram-negative bacteria of monobactams bearing various substituents on oxime residue. Bioorg. Chem., 2020, 94, 103487.
4. Dousheng Zhang, Xia Zhang, Zhiwen Li, Sheng Tang, Zhihao Guo, Changqin Hu, Jingpu Zhang, Danqing Song, Yinghong Li. Comprehensive 2D-Quantitative Structure-Activity Relationship Study on Monobactam Analogues Against Gram-Negative Bacteria. J Biomed Nanotechnol. 2020, 166: 941-953.
5. Zhiwen Li, Junfei Zhu, Junlin He. Conformational studies of 10–23 DNAzyme in solution through pyrenyl-labeled 2′-deoxyadenosine derivatives. Org. Biomol. Chem., 2016, 14 41: 9846.
6. Xiantao Yang, Zhangping Xiao, Junfei Zhu, Zhiwen Li, Junlin He, Lihe Zhang and Zhenjun Yang. Spatial conservation studies of nucleobases in 10–23 DNAzyme by 2′-positioned isonucleotides and enantiomers for increased activity. Org. Biomol. Chem., 2016, 14, 4032-4038.
7. Zhiwen Li, Yang Liu, Gaofeng Liu, Junfei Zhu, Zhibing Zheng, Keliang Liu, Ying Zhou, Junlin He. Position-specific incorporation of imidazolyl group in 10-23 DNAzyme realized catalytic activity enhancement. Bioorg. Med. Chem., 2014, 2215, 4010-4017.
8. Yang Liu, Zhiwen Li, Gaofeng Liu, Qi Wang, Wei Chen, Di Zhang, Maosheng Cheng, Zhibing Zheng, Keliang Liu and Junlin He. Breaking the conservation of guanine residues in the catalytic loop of 10-23 DNAzyme by position-specific nucleobase Modifications for rate enhancement. Chem. Commun. 2013, 49, 5037-5039.
