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研究领域

1. 新颖稳定多肽方法学的开发和生物医学应用: 蛋白-蛋白相互作用 (PPIs) 通常被视为药物发现的非药物性靶点,大多数PPIs包括少于15个氨基酸残基的短螺旋多肽,通过化学手段将多肽稳定在某一固定构象的稳定多肽是重要的调节PPI的代表性化合物。我们课题组的相关研究关注多肽工程战略,致力于发展新型多肽螺旋构象稳定方法,以解释稳定多肽的二级构象对其生物物理性能的影响。与此同时我们通过化学稳定的多肽来研究重要蛋白靶点的生物功能和作用机制,为探索更加有效的药物前体奠定基础。此外,我们还开发了新颖的锍盐策略,应用于蛋白修饰,ADC/PDC/ODC药物构建,活性氨基酸位点归类等多方面工作,已实现快速活细胞标记,基于活细胞的ABPP位点归类等新技术开发。 2. 新颖的可控稳定多肽自组装核酸药物运载体的开发: 核酸类药物是临床上用于治疗病毒感染性疾病、肿瘤、艾滋病的一类重要的药物,以RNAi效应为基础的siRNA药物由于易合成,可以靶向任意蛋白等性质,受到了广泛的关注。但是由于核酸类药物自身容易降解并且不易穿膜,因此迫切需要发展高效并且具有良好生物相容性的核酸运载体。近十年,纳米技术迅速的发展起来,为解决核酸药物的高效传递难题提供了新的思路。研发性能优越并且生物可降解的纳米材料,是将纳米技术推向实际临床应用的关键和难点。多肽作为一类生物体内自身存在的生物分子,具有非常高的生物相容性,并且被证明可以作为有效的核酸运载体,在生物医学领域的应用已经受到极高的关注。团队基于自主开发的“手性诱导螺旋的概念”构建了可以分子间自主装的siRNA运载体C-(RCES5)2和基于“S盐修饰的胞内可逆还原策略”构建了核酸诱导自组装的新型九肽运载体,能够高效的将核酸药物转运到不同的肿瘤细胞中,释放药物,抑制肿瘤生长。 3. 基于锍盐的多肽运载体免疫佐剂的开发: 团队就如何提高肿瘤新抗原肽的免疫激活效果为出发点,提出将新型多肽纳米载体应用到新抗原的递送中,探究多肽纳米材料在肿瘤免疫治疗中的应用潜能。我们创新性的提出利用锍盐中心驱动策略实现免疫佐剂CpG与新抗原肽的可逆共价偶联,并借助核酸佐剂CpG的负电性诱导带有正电锍盐关环多肽材料的快速自组装,获得体系稳定、简单易制备、混合即用、且可包含多条肿瘤新抗原肽的共递送纳米平台。

近期论文

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Na Liu, Dongyuan Wang, ChenshanLian, Rongtong Zhao, LichengTu, Yichi Zhang, Jianbo Liu, Huilin Zhu, Mengying Yu, Chuan Wan, Di Li, Shuiming Li, Feng Yin* and Zigang Li* “Selective Covalent Targeting of Anti‐Apoptotic BFL‐1 by a Sulfonium Tethered Peptide”.ChemBioChem.2021, 22: 340 –344.(Co-Corresponding author, IF:3.16) Yang Li, ChenshanLian, ZhanfengHou, Dongyuan Wang, Rui Wang, Chuan Wan, WanjinZhong, Rongtong Zhao, Yuena Wang, Shuiming Li, Feng Yin* and Zigang Li* “Intramolecular methionine alkylation constructs sulfonium tethered peptides for protein conjugation”. ChemicalCommunications.2020, 56: 3741-3744. (Co-Corresponding author, IF:6.52) ZhanfengHou, Dong-Yuan Wang, Yang Li, Rongtong Zhao, Chuan Wan, Yue Ma, ChenshanLian, Feng Yin* and Zigang Li*”A Sulfonium Triggered Thiol-yne Reaction for Cysteine Modification” J. Org. Chem., 2020,85(3): 1698-1705. (Co-Corresponding author, IF:4.72) Wenjun Li, YuboGao, Jiaona Zhang, Xiaofang Wang, Feng Yin*,Zigang Li*, Min Zhang* “Universal DNA detection realized by peptide based carbon nanotube biosensors ” Nanoscale Adv., 2020, 2: 717-723.(Co-Corresponding author) Fadeng Yang, Wan Zhang, Yixiang Jiang, Feng Yin*, Wei Han* and Zigang Li* “Targeting the amyloid-β fibril surface by constrained helical peptide inhibitor”. Biochemistry.2020, 59(3): 290-296. (Co-Corresponding author, IF:3.37) Yixiang Jiang, Xuehan Jiang, Xiaodong Shi, Fadeng Yang, Yang Cao, Xuan Qin, ZhanfengHou, MingshengXie, Na Liu, Qi Fang, Feng Yin*, Wei Han*, Zigang Li* “α-helical motif as inhibitors of toxic amyloid-β oligomer generation via highly specific recognition of amyloid surface” iScience.2019, 17: 87-100. (Co-Corresponding author) Jianing Zhang, Yue Ma, Kuan Hu, Yuan Feng, Si Chen, Xiaoyang Yang, Jacky Fong-Chuen Loo, Han Zhang, Feng Yin* and Zigang Li* “Surface Coordination of Black Phosphorus with Modified Cisplatin”.Bioconjugate Chemistry.2019, 30(6): 1658-1664. (Co-Corresponding author, IF:4.77) Wang Dongyuan, Yu Mengying, Liu Na, LianChenshan, HouZhanfeng, Wang Rui, Zhao Rongtong, Li Wenjun, Jiang Yixiang, Shi Xiaodong, Li Shuiming, FengYin*,ZigangLi*. A sulfonium tethered peptide ligand rapidly and selectively modifies protein cysteine in vicinity. Chemical Science.2019, 10(19): 4966-4972. (Co-Corresponding author, IF:9.06) Dongyuan Wang, Wenjun Li, Rongtong Zhao, Longjian Chen, Na Liu, Yuan Tian, Hui Zhao, MingshengXie, Fei Lu, Qi Fang, Wei Liang*, Feng Yin*, Zigang Li*.Stabilized peptide HDAC inhibitors derived from HDAC1 substrate H3K56 for the treatment of cancer stem-like cells in vivo. Cancer Research.2019, 79(8): 1769-1783.(Co-Corresponding author, IF: 12.70) Yue Ma, Wenjun Li, Ziyuan Zhou, Xuan Qin, Dongyuan Wang, YuboGao, Zhiqiang Yu, Feng Yin*, and Zigang Li*. “Peptide-AptamerCoassemblyNanocarrier for Cancer Therapy” Bioconjugate Chem., 2019, 30(3): 536-540. (Co-Corresponding author, IF: 4.54) Na Liu, Rongtong Zhao, YueMaa, Dongyuan Wang, Chen Yan, Dongxian Zhou, Feng Yin* and Zigang Li*.The Development of Epigenetics and Related Inhibitors for Targeted Drug Design in Cancer Therapy. Current Topics in Medicinal Chemistry.2018, 18(28): 2380 – 2394. (Co-Corresponding author, IF: 3.24) Zhanfeng Hou, Chengjie Sun, Hao Geng, Kuan Hu, Mingsheng Xie, Yue Ma, Fan Jiang,* Feng Yin,* and Zigang Li* “Facile Chemoselective Modification of Thio-Ethers Generates Chiral Center-Induced Helical Peptides ” Bioconjugate Chemistry. 2018. 29(9): 2904-2908. (Co-Corresponding author, IF: 4.485) Xiaodong Shi, Rongtong Zhao, Yixiang Jiang, Hui Zhao, Yuan Tian, Yanhong Jiang, Jingxu Li, Weirong Qin, Feng Yin* and Zigang Li*. Reversible Stapling of Unprotected Peptides viaChemoselective Methionine Bis-alkylation/Dealkylation.Chemical Science.2018.9:3227-32. (Corresponding author;IF:8.668; Q1) Wenjun Li, Kuan Hu, Qingzhou Zhang, Dongyuan Wang, Yue Ma, ZhanfengHou, Feng Yin*, and Zigang Li. N terminal N-methylation modulates chiral centre induced helical (CIH) peptides’ biophysical properties.Chemistry Communication.2018,54: 1865-8.v(Corresponding author;IF:6.319) Li Wenjun, Wang Dongyuan, Shi Xiaodong, Li Jingxu, Yue Ma, Wang Yanding, Li Tingting, Zhang Jianing, Zhao Rongtong, Yu Zhiqiang, FengYin*and ZigangLi*. A siRNA-induced peptide co-assembly system as a peptide-based siRNAnanocarrier for cancer therapy.Materials Horizons.2018, 5(4): 745-752. (Co-Corresponding author; IF: 13.05) Jingxu Li, Kuan Hu, Hailing Chen, YuJie Wu, Longjian Chen, Feng Yin,* Yuan Tian,* and Zigang Li. In-tether chiral center modulates the proapoptotic activity of KLApeptide. Chemistry Communication.2017, 53: 10452-5.(Corresponding author;IF:6.319)

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