基于DIC/Oxyma的蜘蛛毒素多肽GsMTx4的高效合成及活性评价

doi:10.6023/cjoc202109003

有机化学 ›› 2022, Vol. 42 ›› Issue (2): 498-506.DOI: 10.6023/cjoc202109003 上一篇下一篇

研究论文

基于DIC/Oxyma的蜘蛛毒素多肽GsMTx4的高效合成及活性评价

马艳楠^a, 刘雅妮^a, 王金艳^a, 陈西同^a, 尹昊^a, 迟巧娜^b, 贾世玺^b, 杜姗姗^b^,^c, 齐昀坤^a^,^c^,^*(), 王克威^a^,^c

a 青岛大学药学院山东青岛 266073
b 青岛科技大学化工学院山东青岛 266042
c 青岛大学创新药物研究院山东青岛 266021

收稿日期:2021-09-01 修回日期:2021-09-21 发布日期:2022-02-24
通讯作者: 齐昀坤
作者简介:
^† 共同第一作者
基金资助:
国家自然科学基金(21807063); 国家自然科学基金(82003647); 国家自然科学基金(22177058); 中国博士后科学基金(2019M652307); 中国博士后科学基金(2020T130332); 山东省自然科学基金(ZR2019BH045); 山东省自然科学基金(ZR2020QH100)

DIC/Oxyma Based Efficient Synthesis and Activity Evaluation of Spider Peptide Toxin GsMTx4

Yannan Ma^a, Ya'ni Liu^a, Jinyan Wang^a, Xitong Chen^a, Hao Yin^a, Qiaona Chi^b, Shixi Jia^b, Shanshan Du^b^,^c, Yunkun Qi^a^,^c(), Kewei Wang^a^,^c

a School of Pharmacy, Qingdao University, Qingdao, Shandong 266073
b College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong 266042
c Institute of Innovative Drugs, Qingdao University, Qingdao, Shandong 266021

Received:2021-09-01 Revised:2021-09-21 Published:2022-02-24
Contact: Yunkun Qi
About author:
^† These authors contributed equally to this work.
Supported by:
National Natural Science Foundation of China(21807063); National Natural Science Foundation of China(82003647); National Natural Science Foundation of China(22177058); China Postdoctoral Science Foundation(2019M652307); China Postdoctoral Science Foundation(2020T130332); Natural Science Foundation of Shandong Province(ZR2019BH045); Natural Science Foundation of Shandong Province(ZR2020QH100)

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摘要/Abstract

偶联试剂介导酰胺键形成, 在固相多肽合成中发挥关键作用. 新型DIC (N,N-二异丙基碳二亚胺)/Oxyma (2-肟氰乙酸乙酯)缩合体系具有廉价、操作安全、缩合效率高和抑制消旋等优势, 在手动和自动多肽合成中得到广泛应用. 但是, DIC/Oxyma缩合体系的理想反应比例和温和反应温度尚有待探索. Piezo通道是一种多功能的机械敏感阳离子通道, 与多种遗传性疾病相关, 蜘蛛毒素多肽GsMTx4是目前唯一的特异性靶向Piezo通道的抑制剂. 本研究探索了DIC/Oxyma缩合体系在温和条件下的最佳反应比例, 实现了线性GsMTx4的高效手动固相合成. 通过一次氧化折叠策略构建三对二硫键, 得到活性的GsMTx4. 利用圆二色谱和膜片钳技术等评价GsMTx4的结构和活性. 本工作建立了基于DIC/Oxyma缩合体系的快速、稳健和安全的合成方法, 为固相多肽合成特别是手动固相多肽合成提供了重要方法参考.

关键词: DIC, Oxyma, 固相多肽合成, 二硫键, 氧化折叠, GsMTx4, 多肽毒素

Coupling reagents mediate the formation of amide bonds and play a key role in solid phase peptide synthesis. The novel N,N-diisopropylcarbodiimide (DIC)/ethyl cyanoglyoxylate-2-oxime (Oxyma) condensation system has the advantages of low cost, operational safety, higher coupling efficiency and lower rate of racemization. The DIC/Oxyma condensation system has been widely used in manual and automated synthesis of peptides. However, the ideal reaction ratio in DIC/Oxyma condensation system at mild reaction temperature remains to be further investigated. GsMTx4 is a cysteine rich peptide toxin identified from the venom of Grammostola spatulata spider, which consists of 34 amino acid residues and three pairs of disulfide bonds. GsMTx4 is the only inhibitor specifically targeting piezo channel, which is a multifunctional mechanically sensitive cation channel and associated with a variety of hereditary diseases. Herein, the synthetic efficiencies of different reaction ratios of DIC and Oxyma at moderate reaction temperature were systematically evaluated. The efficiency and robustness of DIC/Oxyma condensation system were validated by the rapid manual synthesis of linear GsMTx4. The one-step oxidative folding strategy was applied for the construction of three pairs of disulfide bridges, affording the active GsMTx4. The circular dichroism and patch-clamp electrophysiology tests were conducted to evaluate the structure and activity of synthetic GsMTx4. In summary, a fast, robust and safe synthetic method based on DIC/Oxyma is established, which is particularly useful for the manual synthesis of peptides.

Key words: DIC, Oxyma, solid phase peptide synthesis, disulfide bond, oxidative folding, GsMTx4, peptide toxin

引用此文

马艳楠, 刘雅妮, 王金艳, 陈西同, 尹昊, 迟巧娜, 贾世玺, 杜姗姗, 齐昀坤, 王克威. 基于DIC/Oxyma的蜘蛛毒素多肽GsMTx4的高效合成及活性评价[J]. 有机化学, 2022, 42(2): 498-506.

Yannan Ma, Ya'ni Liu, Jinyan Wang, Xitong Chen, Hao Yin, Qiaona Chi, Shixi Jia, Shanshan Du, Yunkun Qi, Kewei Wang. DIC/Oxyma Based Efficient Synthesis and Activity Evaluation of Spider Peptide Toxin GsMTx4[J]. Chinese Journal of Organic Chemistry, 2022, 42(2): 498-506.

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图/表 10

图1. HOAt, HOBt, DIC和Oxyma的结构式

Figure 1. Structures of HOAt, HOBt, DIC and Oxyma

图2. DIC/Oxyma缩合体系的反应机理

Figure 2. Reaction mechanism of DIC/Oxyma condensation system

图3. 蜘蛛毒素GsMTx4的氨基酸序列

Figure 3. Amino acid sequence of spider toxin GsMTx4

图4. GsMTx4的固相合成及复性折叠

Figure 4. Solid phase peptide synthesis and oxidative folding of GsMTx4

Linear peptide	Reaction molar ratio	Reaction temperature/℃	HPLC purity/%	Isolated yield/%	Yield/mg
GsMTx4-1	n(Aa)∶n(HCTU)∶n(DIEA)=4∶3.8∶8	28	51	18	37
GsMTx4-2	n(Aa)∶n(DIC)∶n(Oxyma)=4∶8∶4	50	46	16	33
GsMTx4-3	n(Aa)∶n(DIC)∶n(Oxyma)=4∶12∶4	50	41	14	29
GsMTx4-4	n(Aa)∶n(DIC)∶n(Oxyma)=4∶4∶8	50	37	12	25

表1. 线性GsMTx4的合成策略、高效液相色谱纯度及产量

Table 1. Synthetic strategy, HPLC (high performance liquid chromatography) purity and isolated yield of linear GsMTx4

图5. (A) GsMTx4-1, (B) GsMTx4-2, (C) GsMTx4-3和(D) GsMTx4-4的分析型RP-HPLC色谱图和ESI-MS质谱图

Figure 5. Analytical RP-HPLC and ESI-MS spectra of crude peptides and purified peptides of (A) GsMTx4-1, (B) GsMTx4-2, (C) GsMTx4-3 and (D) GsMTx4-4 RP-HPLC conditions: a linear gradient of 5%~60% buffer B [0.08%~0.1% TFA (trifluoroacetic acid) in CH3CN] in buffer A (0.1% TFA in water) over 30 min (5% for 2 min, then 5%~60% for 30 min) on a Vydac C18 column, λ=214 nm

图6. (A) GsMTx4-1、(B) GsMTx4-2、(C) GsMTx4-3和(D) GsMTx4-4的一次氧化折叠RP-HPLC色谱图和ESI-MS质谱图

Figure 6. Analytical RP-HPLC and ESI-MS spectra of one-step oxidative folding process of peptides of (A) GsMTx4-1, (B) GsMTx4-2, (C) GsMTx4-3, and (D) GsMTx4-4 (A) (a)~(b) The RP-HPLC spectra of the folding solution for GsMTx4-1 at 0 min and 12 h, (c) The RP-HPLC and ESI-MS spectra of purified GsMTx4-5. (B) (d)~(e) The RP-HPLC spectra of the folding solution for GsMTx4-2 at 0 min and 12 h, (f) The RP-HPLC and ESI-MS spectra of purified GsMTx4-6. (C) (g)~(h) The RP-HPLC spectra of the folding solution for GsMTx4-3 at 0 min and 12 h, (i) The RP-HPLC and ESI-MS spectra of purified GsMTx4-7. (D) (j)~(k) The RP-HPLC spectra of the folding solution for GsMTx4-4 at 0 min and 12 h, (l) The RP-HPLC and ESI-MS spectra of purified GsMTx4-8. RP-HPLC conditions: a linear gradient of 5%~60% buffer B in buffer A over 30 min (5% for 2 min, then 5%~60% for 30 min) on a Vydac C18 column, λ=214 nm

Linear peptide	Folding product	HPLC purity/%	Isolated yield/%	Yield/mg	Calculated mass	Observed mass
GsMTx4-1	GsMTx4-5	51	28	8.4	4095.90	4094.93
GsMTx4-2	GsMTx4-6	45	24	7.2	4095.90	4094.93
GsMTx4-3	GsMTx4-7	46	25	7.5	4095.90	4095.32
GsMTx4-4	GsMTx4-8	45	25	7.5	4095.90	4094.94

表2. GsMTx4一次氧化折叠的色谱纯度、分离收率及ESI-MS数据

Table 2. HPLC purity, isolated yield and ESI-MS data of one-step oxidative folding strategy for GsMTx4

图7. (A) GsMTx4-5, GsMTx4-6, GsMTx4-7, GsMTx4-8和GsMTx4-9共进样的分析型RP-HPLC色谱图和高分辨ESI-MS质谱图、(B) GsMTx4-1, GsMTx4-5, GsMTx4-6, GsMTx4-7, GsMTx4-8和GsMTx4-9的圆二色谱图

Figure 7. (A) Analytical RP-HPLC and high resolution ESI-MS spectra of GsMTx4-5, GsMTx4-6, GsMTx4-7, GsMTx4-8 and GsMTx4-9 co-injections, and (B) circular dichroism spectra of GsMTx4-1, GsMTx4-5, GsMTx4-6, GsMTx4-7, GsMTx4-8 and GsMTx4-9

图8. 多肽GsMTx4-5、GsMTx4-6、GsMTx4-7、GsMTx4-8、GsMTx4-9和GsMTx4-1对Piezo1通道的抑制作用

Figure 8. Inhibitory effect of peptides GsMTx4-5, GsMTx4-6, GsMTx4-7, GsMTx4-8, GsMTx4-9 and GsMTx4-1 on Piezo1 channel (A)~(F) The typical current traces (Left) and time courses (Right) of Piezo1 currents inhibited by GsMTx4-9, GsMTx4-5, GsMTx4-6, GsMTx4-7, GsMTx4-8 and GsMTx4-1. (G) The normalized inhibition rate of Piezo1 currents by GsMTx4-5, GsMTx4-6, GsMTx4-7, GsMTx4-8, GsMTx4-9 and GsMTx4-1. n=4~6, each data point is represented as mean±SEM, ***p<0.001 (compared with the GsMTx4-1 group), ns: no significance

参考文献 15

[1]	(a) Liu, T.; Xu, S. L.; Zhao, J. F. Chin. J. Org. Chem. 2021, 41, 873. (in Chinese) doi: 10.6023/cjoc202011022 pmid: 26745345
	( 刘涛, 许泗林, 赵军锋, 有机化学, 2021, 41, 873.) doi: 10.6023/cjoc202011022 pmid: 26745345
	(b) Luan, X.; Wu, Y.; Shen, Y. W.; Zhang, H.; Zhou, Y. D.; Chen, H. Z.; Nagle, D. G.; Zhang, W. D. Nat. Prod. Rep. 2021, 38, 7. doi: 10.1039/D0NP00019A pmid: 26745345
	(c) Zhai, C.; Schreiber, C. L.; Padilla-Coley, S.; Oliver, A. G.; Smith, B. D. Angew. Chem., Int. Ed. 2020, 59, 23740. doi: 10.1002/anie.v59.52 pmid: 26745345
	(d) Zhou, X. M.; Zuo, C.; Li, W. Q.; Shi, W. W.; Zhou, X. W.; Wang, H. F.; Chen, S. M.; Du, J. F.; Chen, G. Y.; Zhai, W. J.; Zhao, W. S.; Wu, Y. H.; Qi, Y. M.; Liu, L.; Gao, Y. F. Angew. Chem., Int. Ed. 2020, 59, 15114. doi: 10.1002/anie.v59.35 pmid: 26745345
	(e) Chang, H. N.; Liu, B. Y.; Qi, Y. K.; Zhou, Y.; Chen, Y. P.; Pan, K. M.; Li, W. W.; Zhou, X. M.; Ma, W. W.; Fu, C. Y.; Qi, Y. M.; Liu, L.; Gao, Y. F. Angew. Chem., Int. Ed. 2015, 54, 11760. doi: 10.1002/anie.v54.40 pmid: 26745345
	(f) Vinogradov, A. A.; Yin, Y.; Suga, H. J. Am. Chem. Soc. 2019, 141, 4167. doi: 10.1021/jacs.8b13178 pmid: 26745345
	(g) Uppalapati, M.; Lee, D. J.; Mandal, K.; Li, H.; Miranda, L. P.; Lowitz, J.; Kenney, J.; Adams, J. J.; Ault-Riche, D.; Kent, S. B.; Sidhu, S. S. ACS Chem. Biol. 2016, 11, 1058. doi: 10.1021/acschembio.5b01006 pmid: 26745345
	(h) Silva, O. N.; Torres, M. D. T.; Cao, J.; Alves, E. S. F.; Rodrigues, L. V.; Resende, J. M.; Liao, L. M.; Porto, W. F.; Fensterseifer, I. C. M.; Lu, T. K.; Franco, O. L.; de la Fuente-Nunez, C. Proc. Natl. Acad. Sci. U. S. A. 2020, 117, 26936. doi: 10.1073/pnas.2012379117 pmid: 26745345
[2]	(a) Zheng, J. S.; Tang, S.; Qi, Y. K.; Wang, Z. P.; Liu, L. Nat. Protoc. 2013, 8, 2483. doi: 10.1038/nprot.2013.152 pmid: 32134276
	(b) Sgorbati, C.; Lo Presti, E.; Bergamaschi, G.; Sani, M.; Volonterio, A. J. Org. Chem. 2021, 86, 9225. doi: 10.1021/acs.joc.1c00853 pmid: 32134276
	(c) Kim, H. S.; Lee, Y.; Shin, M. H.; Lim, H. S. Chem. Commun. 2021, 57, 6800. doi: 10.1039/D1CC02848K pmid: 32134276
	(d) Suzuki, R.; Konno, H. Org. Lett. 2020, 22, 3309. doi: 10.1021/acs.orglett.0c00445 pmid: 32134276
	(e) Kent, S. B. H. Chem. Soc. Rev. 2009, 38, 338. doi: 10.1039/B700141J pmid: 32134276
	(f) Akondi, K. B.; Muttenthaler, M.; Dutertre, S.; Kaas, Q.; Craik, D. J.; Lewis, R. J.; Alewood, P. F. Chem. Rev. 2014, 114, 5815. doi: 10.1021/cr400401e pmid: 32134276
	(g) Cui, H. K.; Guo, Y.; He, Y.; Wang, F. L.; Chang, H. N.; Wang, Y. J.; Wu, F. M.; Tian, C. L.; Liu, L. Angew. Chem., Int. Ed. 2013, 52, 9558. doi: 10.1002/anie.v52.36 pmid: 32134276
[3]	(a) Muramatsu, W.; Yamamoto, H. J. Am. Chem. Soc. 2021, 143, 6792. doi: 10.1021/jacs.1c02600
	(b) Muramatsu, W.; Hattori, T.; Yamamoto, H. Chem. Commun. 2021, 57, 6346. doi: 10.1039/D1CC01795K
	(c) Albericio, F.; El-Faham, A. Org. Process Res. Dev. 2018, 22, 760. doi: 10.1021/acs.oprd.8b00159
[4]	(a) Wang, Z.; Wang, X.; Wang, P.; Zhao, J. J. Am. Chem. Soc. 2021, 143, 10374. doi: 10.1021/jacs.1c04614
	(b) Hu, L.; Xu, S.; Zhao, Z.; Yang, Y.; Peng, Z.; Yang, M.; Wang, C.; Zhao, J. J. Am. Chem. Soc. 2016, 138, 13135. doi: 10.1021/jacs.6b07230
[5]	Isidro-Llobet, A.; Kenworthy, M. N.; Mukherjee, S.; Kopach, M. E.; Wegner, K.; Gallou, F.; Smith, A. G.; Roschangar, F. J. Org. Chem. 2019, 84, 4615. doi: 10.1021/acs.joc.8b03001 pmid: 30900880
[6]	Subiros-Funosas, R.; Prohens, R.; Barbas, R.; El-Faham, A.; Albericio, F. Chem. Eur. J. 2009, 15, 9394. doi: 10.1002/chem.v15:37
[7]	Wang, F.; Xu, L.; Chu, G.; Shi, J.; Guo, Q. Chin. J. Org. Chem. 2016, 36, 218. (in Chinese) doi: 10.6023/cjoc201505014
	( 王风亮, 许玲, 储国超, 石景, 郭庆祥, 有机化学, 2016, 36, 218.) doi: 10.6023/cjoc201505014
[8]	(a) Qu, Q.; Pan, M.; Gao, S.; Zheng, Q. Y.; Yu, Y. Y.; Su, J. C.; Li, X.; Hu, H. G. Adv. Sci. 2018, 5, 1800234. doi: 10.1002/advs.v5.7
	(b) Qu, Q.; Gao, S.; Wu, F.; Zhang, M. G.; Li, Y.; Zhang, L. H.; Bierer, D.; Tian, C. L.; Zheng, J. S.; Liu, L. Angew. Chem., Int. Ed. 2020, 59, 6037. doi: 10.1002/anie.v59.15
	(c) Guan, C. J.; Wang, T.; Wang, J.; Li, Y. M. Chin. J. Org. Chem. 2016, 36, 2763. (in Chinese) doi: 10.6023/cjoc201605013
	( 管超建, 王涛, 王君, 李宜明, 有机化学, 2016, 36, 2763.) doi: 10.6023/cjoc201605013
	(d) Huang, Y. C.; Guan, C. J.; Tan, X. L.; Chen, C. C.; Guo, Q. X.; Li, Y. M. Org. Biomol. Chem. 2015, 13, 1500. doi: 10.1039/C4OB02260B
	(e) Liang, L. J.; Chu, G. C.; Qu, Q.; Zuo, C.; Mao, J.; Zheng, Q.; Chen, J.; Meng, X.; Jing, Y.; Deng, H.; Li, Y. M.; Liu, L. Angew. Chem., Int. Ed. 2021, 60, 17171. doi: 10.1002/anie.v60.31
	(f) Zuo, C.; Shi, W.-W.; Chen, X.-X.; Glatz, M.; Riedl, B.; Flamme, I.; Pook, E.; Wang, J.; Fang, G.-M.; Bierer, D.; Liu, L. Sci. China Chem. 2019, 62, 1371. doi: 10.1007/s11426-019-9513-2
[9]	(a) Coste, B.; Mathur, J.; Schmidt, M.; Earley, T. J.; Ranade, S.; Petrus, M. J.; Dubin, A. E.; Patapoutian, A. Science 2010, 330, 55. doi: 10.1126/science.1193270
	(b) Coste, B.; Xiao, B.; Santos, J. S.; Syeda, R.; Grandl, J.; Spencer, K. S.; Kim, S. E.; Schmidt, M.; Mathur, J.; Dubin, A. E.; Montal, M.; Patapoutian, A. Nature 2012, 483, 176. doi: 10.1038/nature10812
[10]	(a) Bae, C.; Gnanasambandam, R.; Nicolai, C.; Sachs, F.; Gottlieb, P. A. Proc. Natl. Acad. Sci. U. S. A. 2013, 110, E1162. pmid: 23695678
	(b) Albuisson, J.; Murthy, S. E.; Bandell, M.; Coste, B.; Louis-Dit-Picard, H.; Mathur, J.; Feneant-Thibault, M.; Tertian, G.; de Jaureguiberry, J. P.; Syfuss, P. Y.; Cahalan, S.; Garcon, L.; Toutain, F.; Simon Rohrlich, P.; Delaunay, J.; Picard, V.; Jeunemaitre, X.; Patapoutian, A. Nat. Commun. 2013, 4, 1884. doi: 10.1038/ncomms2899 pmid: 23695678
[11]	(a) Suchyna, T. M.; Johnson, J. H.; Hamer, K.; Leykam, J. F.; Gage, D. A.; Clemo, H. F.; Baumgarten, C. M.; Sachs, F. J. Gen. Physiol. 2000, 115, 583. doi: 10.1085/jgp.115.5.583 pmid: 10779316
	(b) Ostrow, K. L.; Mammoser, A.; Suchyna, T.; Sachs, F.; Oswald, R.; Kubo, S.; Chino, N.; Gottlieb, P. A. Toxicon 2003, 42, 263. doi: 10.1016/S0041-0101(03)00141-7 pmid: 10779316
[12]	(a) Qu, Q.; Gao, S.; Li, Y. M. J. Pept. Sci. 2018, 24, e3112. doi: 10.1002/psc.v24.8-9
	(b) Zhu, W.; Hou, F.; Fang, J.; Bahrani Fard, M. R.; Liu, Y.; Ren, S.; Wu, S.; Qi, Y.; Sui, S.; Read, A. T.; Sherwood, J. M.; Zou, W.; Yu, H.; Zhang, J.; Overby, D. R.; Wang, N.; Ethier, C. R.; Wang, K. iScience 2021, 24, 102042. doi: 10.1016/j.isci.2021.102042
[13]	(a) Fang, G. M.; Wang, J. X.; Liu, L. Angew. Chem., Int. Ed. 2012, 51, 10347. doi: 10.1002/anie.201203843
	(b) Fang, G. M.; Li, Y. M.; Shen, F.; Huang, Y. C.; Li, J. B.; Lin, Y.; Cui, H. K.; Liu, L. Angew. Chem., Int. Ed. 2011, 50, 7645. doi: 10.1002/anie.201100996
	(c) Huang, Y. C.; Li, Y. M.; Chen, Y.; Pan, M.; Li, Y. T.; Yu, L.; Guo, Q. X.; Liu, L. Angew. Chem., Int. Ed. 2013, 52, 4858. doi: 10.1002/anie.v52.18
[14]	(a) Pan, M.; Gao, S.; Zheng, Y.; Tan, X.; Lan, H.; Tan, X.; Sun, D.; Lu, L.; Wang, T.; Zheng, Q.; Huang, Y.; Wang, J.; Liu, L. J. Am. Chem. Soc. 2016, 138, 7429. doi: 10.1021/jacs.6b04031
	(b) Chen, X. T.; Wang, J. Y.; Ma, Y. N.; Dong, L. Y.; Jia, S. X.; Yin, H.; Fu, X. Y.; Du, S. S.; Qi, Y. K.; Wang, K. J. Pept. Sci. 2021, e3368.
[15]	(a) Wang, J.; Dong, L.; Liu, Y.; Chen, X.; Ma, Y.; Yin, H.; Du, S.; Qi, Y.; Wang, K. Chin. J. Org. Chem. 2021, 41, 2800. (in Chinese) doi: 10.6023/cjoc202102045
	( 王金艳, 董黎颖, 刘雅妮, 陈西同, 马艳楠, 尹昊, 杜姗姗, 齐昀坤, 王克威, 有机化学, 2021, 41, 2800.) doi: 10.6023/cjoc202102045
	(b) Tang, S.; Zuo, C.; Huang, D. L.; Cai, X. Y.; Zhang, L. H.; Tian, C. L.; Zheng, J. S.; Liu, L. Nat. Protoc. 2017, 12, 2554. doi: 10.1038/nprot.2017.129
	(c) Li, J. B.; Qi, Y. K.; He, Q. Q.; Ai, H. S.; Liu, S. L.; Wang, J. X.; Zheng, J. S.; Liu, L.; Tian, C. Cell Res. 2018, 28, 257. doi: 10.1038/cr.2017.157

基于DIC/Oxyma的蜘蛛毒素多肽GsMTx4的高效合成及活性评价

DIC/Oxyma Based Efficient Synthesis and Activity Evaluation of Spider Peptide Toxin GsMTx4

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