基于疾病靶向的多肽-药物偶联物的设计策略及药物研究

主持项目：

1. 国家自然科学基金青年项目(21602092)，新型肽类基因载体的设计及其在基因编辑治疗中的应用评价，2017/01-2019/12。

2. 中央高校基本科研业务费专项资金自由探索项目(lzujbky-2017-120)，新型可降解肽类基因载体的设计及在基因治疗中的应用，2017/01-2018/12。

3. 中央高校基本科研业务费专项资金自由探索项目(lzujbky-2015-281)，新型靶向穿膜肽的设计及抗肿瘤应用，2015/07-2016/12。

研究成果：

1. Song JJ, Ma PP, Huang SJ, Wang JL, Xie H, Jia B, Zhang W. Acylation of the antimicrobial peptide CAMEL for cancer gene therapy. Drug Deliv. 2020 Dec;27(1):964-973

2. Song JJ, Huang SJ, Zhang ZZ, 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 Dec;27(1):91-99.

3. Song JJ, Huang SJ, Ma PP, Zhang B, Jia B, Zhang W. Improving NK1R-targeted gene delivery of stearyl-antimicrobial peptide CAMEL by conjugating it with substance P. Bioorg Med Chem Lett. 2020 Aug 15;30(16):127353.

4. Zhang Y, Li L, Chang LL, Liu H, Song JJ, Liu Y, Bao HX, Liu BJ, Wang R , Ni JM. Design of a new pH-activatable cell-penetrating peptide for drug delivery into tumor cells. Chem Biol Drug Des. 2019 Sep;94(5):1884-1893.

5. Kai M，Zhang W，Xie H，Liu 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. Chinese Chemical Letters. 2018, 29:1163-9. (共同通讯)

6. Zheng T, Zhang R, Zhang T, Zhang M, Xu B, Song JJ, Li N, Tang HH, Wang P, Wang R, Fang Q. CB1 cannabinoid receptor agonist mouse VD-hemopressin(α) produced supraspinal analgesic activity in the preclinical models of pain. Brain Res. 2018 Feb 1;1680:155-164.

7. Wang Z, Pan JX, Song JJ, Tang HH, Yu HP, Li X, Li N, Zhang T, Zhang R, Zhang M, Xu B, Fang Q, Wang R. Structure-Based Optimization of Multifunctional Agonists for Opioid and Neuropeptide FF Receptors with Potent Nontolerance Forming Analgesic Activities. J Med Chem. 2016 Nov 23;59(22):10198-10208.

8. Wang Z, Li N, Wang P, Tang HH, Han Z, Song JJ, Li X, Yu H, Zhang T, Zhang R, Xu B, Zhang MN, Fang Q, Wang R. Pharmacological characterization of EN-9, a novel chimeric peptide of endomorphin-2 and neuropeptide FF that produces potent antinociceptive activity and limited tolerance. Neuropharmacology. 2016 Sep;108:364-72.

9. Li N, Han Z, Wang Z, Xing Y, Sun Y, Li X, Song JJ, Zhang T, Zhang R, Zhang M, Xu B, Fang Q, Wang R. BN-9, a chimeric peptide with mixed opioid and neuropeptide FF receptor agonistic properties, produces nontolerance-forming antinociception in mice. Br J Pharmacol. 2016 Jun;173(11):1864-80.

10. Song JJ, Zhang Y, Zhang W, Chen J, Yang X, Ma PP, Zhang B, Liu B, Ni JM*, Wang R*. Cell penetrating peptide TAT can kill cancer cells via membrane disruption after attachment of camptothecin. Peptides. 2015，63:143-9.

11. Chen G, Song JJ, 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.

12. Zhang Y, Song JJ, 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.

13. Song JJ , Zhang W , 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.

14. 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)

15. Zhang W1, Song JJ1, 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)

16. 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.

17. 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)

18. 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)

专利成果：

1. 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

2. 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

3. 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