1.基于神经肽的药物研究

神经肽是一类内源性活性物质，具有多种多样的生理调节功能。本课题组主要从事神经肽在抗菌、促伤口愈合以及肿瘤靶向等方面的应用研究。通过发展新型多肽修饰策略、构效关系研究以及成药性评价等手段获得具有临床应用前景的神经肽类药物，用于慢性伤口和肿瘤的治疗。

2.多肽-药物偶联物的设计策略及药物研究

靶向多肽分子能够使相连的药物分子具有更优的药代动力学、药效学、选择性和安全性。本课题组通过发展新型的靶向多肽修饰策略、靶向多肽分子筛选策略以及靶向屏蔽策略等构建具有临床应用前景的多肽-药物偶联物，用于肿瘤和炎症的治疗。

主持的科研项目：

1. 主持国家自然科学基金面上项目一项(81773566)，一种新型伤口愈合肽的设计及其在糖尿病足治疗中的应用研究，2018/01-2021/12。

2. 主持国家自然科学基金青年项目一项(81402776)，磁靶向抗菌肽的设计、合成以及抗肿瘤研究，2015/01-2017/12。

3. 主持中国博士后科学基金特别资助项目一项(2013T60896)，双功能抗菌肽的设计及抗菌活性研究，2013/05-2014/12。

4. 主持中国博士后科学基金面上项目一项(2012M512047)，新型酸激活基因载体的设计及应用，2012/05-2013/12。

参与的科研项目：

1. 以项目组主要成员参与国家自然科学基金面上项目一项(81773564)，采用分子桥键化等策略构建高效稳定的α-螺旋型抗菌肽构效关系研究，2018/01-2021/12。

2. 以项目组主要成员参与高等学校博士学科点专项科研基金(优先发展领域)一项(20130211130005)，高酶解稳定性速激肽-1类似物的设计及抗菌和抗炎活性研究，2014/01-2016/12。

3. 以项目组主要成员参与国家自然科学基金青年项目一项(81202400)，基于分子靶向与电荷屏蔽协同修饰的新型低毒抗菌肽的设计及其抗肿瘤应用，2013/01-2015/12。

4. 以项目组主要成员参与国家自然科学基金面上项目一项(81273440)，高稳定性酸敏感穿膜肽的设计与应用，2013/01-2016/12。

发表论文：

1. Sujie Huang, Yuxuan Gao, Ling Ma, Bo Jia, Wenhao Zhao, Yufan Yao, Wenyuan Li, Tongyi Lin, Rui Wang, Jingjing Song*, Wei Zhang*. Design of pH-responsive antimicrobial peptide melittin analog-camptothecin conjugates for tumor therapy. Asian J Pharm Sci. 2024;19(1):100890.
2. Kun Ji, Yufan Yao, Yuxuan Gao, Sujie Huang, Ling Ma, Qing Pan, Jun Wu, Wei Zhang*, Hongmei Chen*, Lei Zhang*. Evaluating the cytotoxicity mechanism of the cell-penetrating peptide TP10 on Jurkat cells. Biochimie. 2024:221:182-192. 
3. Yufan Yao, Wei Zhang*, Sisi Li, Huan Xie, Zhengzheng Zhang, Bo Jia, Sujie Huang, Wenyuan Li, Ling Ma, Yuxuan Gao, Jingjing Song*, Rui Wang*. Development of Neuropeptide Hemokinin-1 Analogues with Antimicrobial and Wound-Healing Activity. J Med Chem. 2023;66(10):6617-6630.
4. Ling Ma, Sujie Huang, Huan Xie, Panpan Ma, Bo Jia, Yufan Yao, Yuxuan Gao, Wenyuan Li, Jingjing Song*, Wei Zhang*. Influence of chain length on the anticancer activity of the antimicrobial peptide CAMEL with fatty acid modification. Eur J Med Chem. 2022;239:114557.
5. Kui Liu, Long Fan, Sujie Huang, Jie Sun, Xiaofeng Wang, Huixue Li, Changdai Si, Wei Zhang*, Tianrong Li*, Zhengyin Yang*. A benzocoumarin-based fluorescent probe for ultra-sensitive and fast detection of endogenous/exogenous hypochlorous acid and its applications. Analyst. 2022;147(9):1976-1985.
6. Zhongwen Zhu, Yufan Yao, Sujie Huang, Ling Ma, Jingjing Song*, Wei Zhang*. Antimicrobial and anti-inflammatory activities of the neuropeptide antagonist SPA. J Pept Sci. 2022;28(7):e3402.
7. Sujie Huang, Zhongwen Zhu, Bo Jia, Wei Zhang*, Jingjing Song*. Design of acid-activated cell-penetrating peptides with nuclear localization capacity for anticancer drug delivery. J Pept Sci. 2021 Oct;27(10):e3354.
8. Jingjing Song, Sujie Huang, Panpan Ma, Bao Zhang, Bo Jia, Wei Zhang*. Improving NK1R-targeted gene delivery of stearyl-antimicrobial peptide CAMEL by conjugating it with substance P. Bioorg Med Chem Lett. 2020;30(16):127353.
9. Jingjing Song, Panpan Ma, Sujie Huang, Juanli Wang, Huan Xie, Bo Jia, Wei Zhang*. Acylation of the antimicrobial peptide CAMEL for cancer gene therapy. Drug Deliv. 2020;27(1):964-973.
10. Song J, Huang S, Zhang Z, Jia B, Xie H, Kai M, Zhang W*. SPA: a peptide antagonist that acts as a cell-penetrating peptide for drug delivery. Drug Deliv. 2020;27(1):91-99.
11. Ji K, Xiao Y, Zhang W*. Acid-activated nonviral peptide vector for gene delivery. J Pept Sci. 2019:e3230.
12. Kai M, Zhang W, Xie H, LW, Huang SJ, Li X, Zhang ZZ, Liu YY, Zhang BZ, Song JJ*, Wang R*. Effects of linker amino acids on the potency and selectivity of dimeric antimicrobial peptides. Chin Chem Lett. 2018;29 (7):1163–1166
13. Khan WU, Wang D, Zhang W, Tang Z, Ma X, Ding X, Du S, Wang Y*. High Quantum Yield Green-Emitting Carbon Dots for Fe(ІІІ)Detection, Biocompatible Fluorescent Ink and Cellular Imaging. Sci Rep. 2017;7(1):14866.
14. Liu B, Zhang W, Gou S, Huang H, Yao J, Yang Z, Liu H, Zhong C, Liu B, Ni J, Wang R*. Intramolecular cyclization of the antimicrobial peptide Polybia-MPI with triazole stapling: influence on stability and bioactivity. J Pept Sci. 2017;23(11):824-832.
15. Li J, Zeng Q, Zhang Y, Li X, Hu H1, Miao X, Yang W, Zhang W, Song X, Mou L, Wang R*. Neurokinin-1 receptor mediated breast cancer cell migration by increased expression of MMP-2 and MMP-14. Eur J Cell Biol. 2016;95(10):368-377.
16. Zhang W, Yang X, Song J, Zheng X, Chen J, Ma P, Zhang B, Wang R*. Conjugation with Acridines Turns Nuclear Localization Sequence into Highly Active Antimicrobial Peptide. Engineering. 2015;1 (4): 500-505 .
17. Chen G, Song J, Zhang H, Jiang Y, Liu W, Zhang W*, Wang B*. Pd nanoparticles encapsulated in magnetic carbon nanocages: an efficient nanoenzyme for the selective detection and multicolor imaging of cancer cells. Nanoscale. 2015;7:14393-400.
18. Xie J, Gou Y, Zhao Q, Li S, Zhang W, Song J, Mou L, Li J, Wang K, Zhang B, Yang W, Wang R*. Antimicrobial activities and action mechanism studies of transportan 10 and its analogues against multidrug-resistant bacteria. J Pept Sci. 2015;21(7):599-607.
19. Song J, Zhang Y, Zhang W, Chen J, Yang X, Ma P, Zhang B, Liu B, Ni J*, Wang R*. Cell penetrating peptide TAT can kill cancer cells via membrane disruption after attachment of camptothecin. Peptides. 2015;63:143-9.
20. Liu H, Zhang W, Ma L, Fan L, Gao F, Ni J*, Wang R*. The improved blood-brain barrier permeability of endomorphin-1 using the cell-penetrating peptide synB3 with three different linkages. Int J Pharm. 2014;476(1-2):1-8.
21. Liu J, Zuo W, Zhang W, Liu J, Wang Z, Yang Z, Wang B*. Europium(III) complex-functionalized magnetic nanoparticle as a chemosensor for ultrasensitive detection and removal of copper(II) from aqueous solution. Nanoscale. 2014;6(19):11473-8.
22. Xie J, Gou Y, Zhao Q, Wang K, Yang X, Yan J, Zhang W, Zhang B, Ma C, Wang R*. Antimicrobial activities and membrane-active mechanism of CPF-C1 against multidrug-resistant bacteria, a novel antimicrobial peptide derived from skin secretions of the tetraploid frog Xenopus clivii. J Pept Sci. 2014;20(11):876-84.
23. Zhang Y, Song J, Zhang W, Liang R, Ma Y, Zhang L, Wei X, Ni J*, Wang R*. Functional properties of a novel hybrid antimicrobial peptide NS: potent antitumor activity and efficient plasmid delivery. J Pept Sci. 2014;20(10):785-93.
24. Zhang W ¹, Song JJ ¹, Liang RR, Zheng X, Chen JB, Li GL, Zhang BZ, Yan X, Wang R*. Stearylated antimicrobial peptide melittin and its retro isomer for efficient gene transfection. Bioconjugate Chem, 2013, 24:1805-1812. (共同一作)
25. 张伟, 宋竟婧, 张邦治, 杨雯乐, 王 锐*. 多肽新药研发策略的研究进展. 中国科学:化学, 2013, 43, 939-940.
26. Zhang W¹, Song JJ ¹, Liang RR, Zheng X, Chen JB, Li GL, Zhang BZ, Wang KR, Yan X, Wang R*. Stearylated antimicrobial peptide [D]-K6L9 with cell penetrating property for efficient gene transfer. Peptides, 2013, 46C:33-39. (共同一作)
27. Song JJ ¹, Zhang W ¹, Kai M, Chen J, Liang R, Zheng X, Li G, Zhang B, Wang K, Zhang Y, Yang Z, Ni J, Wang R. Design of an Acid-Activated Antimicrobial Peptide for Tumor Therapy. Mol Pharm. 2013,10: 2934-2941. (共同一作)
28. Xing Y ¹, Zhang W ¹, Song J, Zhang Y, Jiang X, Wang R. Anticancer effects of a novel class rosin-derivatives with different mechanisms. Bioorg Med Chem Lett, 2013, 23:3868-72. (共同一作)
29. Liu J, Zhang W, Zhang H, Yang Z, Li T, Wang BD*, Huo X, Wang R, Chen H. A multifunctional nanoprobe based on Au-Fe3O4 nanoparticles for multimodal and ultrasensitive detection of cancer cells. Chem Commun (Camb), 2013, 49:4938-40.
30. Zhi LH, Liu J, Wang Y, Zhang W, Wang BD*, Xu ZG, Yang ZY, Huo X, Li GM. Multifunctional Fe3O4 nanoparticles for highly sensitive detection and removel of Al(III) in aqueous solution. Nanoscale, 2013, 5:1552-1556.
31. Wang K, Yan J, Dang W, Liu X, Chen R, Zhang J, Zhang B, Zhang W, Kai M, Yan W, Yang Z, Xie J, Wang R*. Membrane active antimicrobial activity and molecular dynamics study of a novel cationic antimicrobial peptide polybia-MPI, from the venom of Polybia paulista. Peptides, 2013, 39:80-88.
32. Wang KR, Yan JX, Chen R, Dang W, Zhang BZ, Zhang W, Song JJ, Wang R*. Membrane-active action mode of Polybia-CP, a novel antimicrobial peptide isolated from the venom of Polybia Paulista. Antimicrob Agents Chemother, 2012, 56:3318-3323.
33. Yan JX, Wang KR, Chen R, Song JJ, Zhang BZ, Dang W, Zhang W, Wang R*. Membrane active antitumor activity of NK-18, a mammalian NK-lysin-derived cationic antimicrobial peptide. Biochimie, 2012, 94:184-191.
34. Zhang W¹, Song JJ¹, Zhang BZ, Liu LW, Wang KR, Wang R*. Design of acid-activated cell penetrating peptide for delivery of active molecules into cancer cells. Bioconjugate Chem, 2011, 22:1410-1415. (共同一作)
35. Zhang W¹, Song JJ¹, Mu LY, Zhang BZ, Liu LW, Xing YH, Wang KR, Li ZY, Wang R*. Improving anticancer activity and selectivity of camptothecin through conjugation with releasable substance P. Bioorg Med Chem Lett, 2011, 21:1452-1455. (共同一作)
36. Song JJ, Kai M, Zhang W, Zhang JD, Liu LW, Zhang BZ, Liu X, Wang R*. Cellular uptake of transportan 10 and its analogs in live cells: Selectivity and structure–activity relationship studies. Peptides, 2011, 32:1934-1941.
37. Wang KR, Yan JX, Liu X, Zhang JD, Chen R, Zhang BZ, Dang W, Zhang W, Kai M, Song Jingjing, Wang R*. Novel cytotoxity exhibition mode of polybia-CP, a novel antimicrobial peptide from the venom of the social wasp Polybia paulista. Toxicology, 2011, 288:27-33.
38. Zhang W, Li J, Liu LW, Wang KR, Song Jingjing, Yan JX, Li ZY, Zhang BZ, Wang R*. A novel analog of antimicrobial peptide Polybia-MPI, with thioamide bond substitution, exhibits increased therapeutic efficacy against cancer and diminished toxicity in mice. Peptides, 2010, 31:1832-1838.
39. Zhang BZ, Wang KR, Yan JX, Zhang W, Song Jingjing, Ni JM, Wang R*. In vitro and in vivo antitumor effects of novel actinomycin D analogs with amino acid substituted in the cyclic depsipeptides. Peptides, 2010, 31:568-573.
40. Wang KR, Zhang BZ, Zhang W, Yan JX, Li XL, Wang R*. Potent antitumor effects of a novel actinomycin D analog Leu5AMD. Cancer Lett, 2008, 268:38-45.
41. Wang KR, Zhang BZ, Zhang W, Yan JX, Li J, Wang R*. Antitumor effects, cell selectivity and structure-activity relationship of a novel antimicrobial peptide polybia-MPI. Peptides, 2008, 29:963-938.

参编书籍：

1. 张伟，张邦治，谢俊秋，王锐，抗菌肽设计的研究进展，化学工业出版社， 2015.04.01。

2. 方泉，张伟，王锐，多肽科学研究进展，中国科学技术出版社， 2014.02.01

专利方面成果：

1. 王锐，宋竟婧，张伟，开明，张邦治，具有酸激活特性的抗菌肽AMitP及其合成和在制备抗肿瘤药物中的应用，国家发明专利，授权专利号：ZL201210221080.4，授权公告日：2014.04.02

2. 王锐，张伟，宋竟婧，张邦治，基于N末端18烷酰化抗菌肽构建的非病毒基因载体，国家发明专利，申请专利号：201210221082.3专利申请日：2012.06.29

3. 王锐，宋竟婧，张伟，张邦治，一种具有多靶点的抗菌多肽偶联物及其二聚物的合成和应用，国家发明专利，授权专利号：ZL 201510406998X，授权公告日：2018.01.19