Efficient Synthesis and Oxidative Folding Studies of Centipede Toxin RhTx

doi:10.6023/cjoc202102045

Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (7): 2800-2809.DOI: 10.6023/cjoc202102045 Previous Articles Next Articles

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蜈蚣毒素多肽RhTx的高效化学合成及复性折叠研究

王金艳^a, 董黎颖^a, 刘雅妮^a, 陈西同^a, 马艳楠^a, 尹昊^a, 杜姗姗^b^,^*(), 齐昀坤^a^,^*(), 王克威^a

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

收稿日期:2021-02-24 修回日期:2021-03-24 发布日期:2021-04-12
通讯作者: 杜姗姗, 齐昀坤
作者简介:
† 共同第一作者(These authors contributed equally to this work).
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(81870653); 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)

Efficient Synthesis and Oxidative Folding Studies of Centipede Toxin RhTx

Jinyan Wang^a, Liying Dong^a, Ya'ni Liu^a, Xitong Chen^a, Yannan Ma^a, Hao Yin^a, Shanshan Du^b(), Yunkun Qi^a(), Kewei Wang^a

a School of Pharmacy, Qingdao University, Qingdao, Shandong 266073
b College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong 266042

Received:2021-02-24 Revised:2021-03-24 Published:2021-04-12
Contact: Shanshan Du, Yunkun Qi
Supported by:
National Natural Science Foundation of China(21807063); National Natural Science Foundation of China(82003647); National Natural Science Foundation of China(81870653); 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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Abstract

The critical step for the synthesis of disulfide-containing peptides is the efficient construction of one or multiple disulfide bridges. Generally, the folding of disulfide bonds could be achieved by three chemical strategies,i.e. one-step oxidative folding strategy, multi-step oxidative folding strategy, and one-pot oxidative folding strategy. Because few comparative studies have been conducted on efficiencies of three strategies, the systematical research is desirable. Three folding strategies were separately applied for the preparation of centipede toxin RhTx. The results showed that the isolated yield of two-step oxidative folding strategy was higher than those of one-step and one-pot oxidative folding strategies. Besides, the one-pot oxidative folding strategy may induce severe misfoldings. The circular dichroism (CD) and activity tests indicated that disulfide bonds are critical for the structure and activity of RhTx. In addition, the efficient preparation of RhTx on tens of milligrams scale was achieved, affording molecular tools for the further biological and biophysical studies of RhTx targeting TRPV1. Overall, three mainstream oxidative folding strategies were systematically studied, which provided a valuable reference for the synthesis of disulfide-containing peptides.

Key words: disulfide bond, disulfide-containing peptide, oxidative folding, RhTx, solid phase peptide synthesis, thiol protecting group

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Jinyan Wang, Liying Dong, Ya'ni Liu, Xitong Chen, Yannan Ma, Hao Yin, Shanshan Du, Yunkun Qi, Kewei Wang. Efficient Synthesis and Oxidative Folding Studies of Centipede Toxin RhTx[J]. Chinese Journal of Organic Chemistry, 2021, 41(7): 2800-2809.

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Fig. & Tab. 6

Figure 1. (A) Amino acid sequences of RhTx, (B) synthetic route and one-step oxidative folding strategy of linear peptide 1, (C) two-step oxidative folding strategy of linear peptide 2, (D) one-pot oxidative folding strategy of linear peptide 2, (E) two-step oxidative folding strategy of linear peptide 3 and (F) one-pot oxidative folding strategy of linear peptide 3

Figure 2. Analytical RP-HPLC chromatogram of one-step oxidative folding process of peptide 1 (λ=214 nm) (a)~(c) RP-HPLC spectra of folding solution for peptide 1. (d) RP-HPLC and ESI-MS spectra of purified peptide 4. The spectrum gave an observed mass of 2964.7 Da (calculated 2965.5 Da, average isotopes). RP-HPLC condition: a linear gradient of 10%~60% buffer B (0.08%~0.1% TFA in CH3CN) in buffer A (0.1% TFA in water) over 30 min (10% for 1 min, then 10%~60% for 30 min) on a Vydac C18 column

Figure 3. Analytical RP-HPLC chromatogram of two-step oxidative folding process of peptide 2 (A) and peptide 3 (B) (λ=214 nm) (a)~(c) RP-HPLC spectra of the folding solution for peptide 2 at 0, 10 and 45 min. (d) RP-HPLC and ESI-MS spectra of purified peptide 5. The ESI-MS spectrum gave an observed mass of 3109.5 Da (calculated 3109.4 Da, average isotopes). (e)~(f) RP-HPLC spectra of the folding solution for peptide 5 at 5 and 15 min. (g) RP-HPLC and ESI-MS spectra of purified peptide 6. The ESI-MS spectrum gave an observed mass of 2964.7 Da (calculated 2965.5 Da, average isotopes). (h)~(j) RP-HPLC spectra of the folding solution for peptide 3 at 0, 10 and 45 min. (k) RP-HPLC and ESI-MS spectra of purified peptide 7. The spectrum gave an observed mass of 3108.5 Da (calculated 3109.4 Da, average isotopes). (l)~(m) RP-HPLC spectra of the folding solution for peptide 7 at 5 and 15 min. (n) RP-HPLC and ESI-MS spectra of purified peptide 8. The spectrum gave an observed mass of 2964.7 Da (calculated 2965.5 Da, average isotopes). RP-HPLC condition: a linear gradient of 10%~60% buffer B in buffer A over 30 min (10% for 2 min, then 10%~60% for 30 min) on a Vydac C4 column

Figure 4. Analytical RP-HPLC chromatogram of one-pot oxidative folding process of peptide 2 (A) and peptide 3 (B) (λ=214 nm) (a)~(d) RP-HPLC spectra of the folding solution for peptide 2 at 0, 15 min, 18 and 24 h. For peptide 9: the ESI-MS spectrum gave an observed mass of 3109.0 Da (calculated 3109.4 Da, average isotopes). (e)~(f) RP-HPLC spectra of the folding solution for peptide 9 at 30 and 60 min. (g) RP-HPLC and ESI-MS spectra of purified peptide 10. The ESI-MS spectrum gave an observed mass of 2964.8 Da (calculated 2965.5 Da, average isotopes). (h)~(k) RP-HPLC spectra of the folding solution for peptide 3 at 0, 15 min, 18 and 24 h. For peptide 11: the ESI-MS spectrum gave an observed mass of 3108.5 Da (calculated 3109.4 Da, average isotopes). (l)~(m) RP-HPLC spectra of the folding solution for peptide 11 at 30 and 90 min. (n) RP-HPLC and ESI-MS spectra of purified peptide 12. The ESI-MS spectrum gave an observed mass of 2964.8 Da (calculated 2965.5 Da, average isotopes). RP-HPLC condition: a linear gradient of 10%~60% buffer B in buffer A over 30 min (10% for 2 min, then 10%~60% for 30 min) on a Vydac C4 column

Figure 5. (A) Analytical RP-HPLC and ESI-MS spectra of peptides 4, 6, 8, 10 and 12 co-injections and (B) circular dichroism (CD) spectra of peptides 1, 4, 6, 8, 10 and 12 The ESI-MS spectrum gave an observed mass of 2964.8 Da (calculated 2965.5 Da, average isotopes). RP-HPLC condition: a linear gradient of 10%~60% buffer B in buffer A over 30 min (10% for 1 min, then 10%~60% for 30 min) on a Vydac C18 column, λ=214 nm

Figure 6. Agonistic effect of peptides 4, 6, 8, 10 and 12 on TRPV1 TRPV1 stably-transfected CHO cells were held at -60 mV and followed by a voltage ramp from –100 mV to +100 mV with 2 s intervals. (A~F) the time courses of TRPV1 currents recorded at +100 mV induced by peptides 1,4,6,8,10,12, and capsaicin (Cap). (G) The normalized currents of peptides 4,6,8,10,12 and linear peptide 1 by capsaicin. n=3~6, data were expresses as mean±SEM, *** p<0.001 vs. capsaicin,###p<0.001 vs. linear peptide 1. ns, no significance

References 10

[10]	(f) Wu, Y; Wu, X.; Zhangsun, D.; Luo, S. Biotechnol. Bull. 2013, 7,184 (in Chinese).
	( 吴勇, 吴潇洒, 长孙东亭, 罗素兰, 生物技术通报, 2013, 7,184.)
[11]	(a) Cuthbertson, A.; Indrevoll, B. Org. Lett. 2003, 5,2955. doi: 10.1021/ol035105w
	(b) Naraga,A. M.B.; Belleza,O. J.V.; Villaraza,A. J.L. RSC Adv. 2018, 8,36579. doi: 10.1039/C8RA03706J
	(c) Khemtémourian, L.; Desbenoit, N; Mahesh, P.; Chatterjee, S.; Deschemin,J. -C.; Vaulont, S.; Tomas, A.; Sari,M. -A.; Artaud, I. Protein Pept. Lett. 2012, 19,219. doi: 10.2174/092986612799080167
[12]	(a) 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
	(b) Guo, Y.; Sun,D. -M.; Wang,F. -L.; He, Y.; Liu, L.; Tian,C. -L. Angew. Chem.,Int. Ed. 2015, 54,14276. doi: 10.1002/anie.201500699
	(c) Xu, Y.; Wang, T.; Guan,C. -J.; Li,Y. -M.; Liu, L.; Shi, J.; Bierer, D. Tetrahedron Lett. 2017, 58,1677. doi: 10.1016/j.tetlet.2017.03.024
	(d) Wang, T.; Fan, J.; Chen,X. -X.; Zhao, R.; Xu, Y.; Bierer, D.; Liu, L.; Li,Y. -M.; Shi, J.; Fang,G. -M. Org. Lett. 2018, 20,6074. doi: 10.1021/acs.orglett.8b02459
	(e) Qi,Y. -K.; Qu, Q.; Bierer, D.; Liu, L. Chem.-Asian J. 2020, 15,2793. doi: 10.1002/asia.v15.18
	(f) 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
	(g) Chen, J.; Sun, S.; Zhao, R.; Xi,C. -P.; Qiu, W.; Wang, N.; Wang, Y.; Bierer, D.; Shi, J.; Li,Y. -M. ChemistrySelect 2020, 5,1359. doi: 10.1002/slct.v5.4
	(h) Guo, Y.; Liu, C.; Song, H.; Wang,F. -L.; Zou, Y.; Wu,Q. -Y.; Hu,H. -G. RSC Adv. 2017, 7,2110. doi: 10.1039/C6RA26617G
	(i) Huang,D. -L.; Bai,J. -S.; Wu, M.; Wang, X.; Riedl, B.; Pook, E.; Alt, C.; Erny, M.; Li,Y. -M.; Bierer, D.; Shi, J.; Fang,G. -M. Chem. Commun. 2019, 55,2821. doi: 10.1039/C9CC00328B
	(j) Wang,F. -L.; Guo, Y.; Li,S. -J.; Guo,Q. -X.; Shi, J.; Li,Y. -M. Org. Biomol. Chem. 2015, 13,6286. doi: 10.1039/C5OB00741K
	(k) Wang, T.; Kong,Y. -F.; Xu, Y.; Fan, J.; Xu,H. -J.; Bierer, D.; Wang, J.; Shi, J.; Li,Y. -M. Tetrahedron Lett. 2017, 58,3970. doi: 10.1016/j.tetlet.2017.09.006
[1]	(a) Daly,N. L.; Craik,D. J. Curr. Opin. Chem. Biol. 2011, 15,362. doi: 10.1016/j.cbpa.2011.02.008
	(b) Silva,P. M.; Gonçalves, S.; Santos,N. C. Front. Microbiol. 2014, 5,97.
	(c) Tanemura, Y.; Mochizuki, Y.; Kumachi, S.; Nemoto, N. Biology 2015, 4,161. doi: 10.3390/biology4010161
	(d) Wu, Q.; Liu, Z.; Fu, C.; Lin, Y.; Dai, Q. Chin. J. Org. Chem. 2010, 30,1517 (in Chinese). doi: 10.1002/cjoc.v30.7
	( 吴巧玲, 刘珠果, 付超, 林原斌, 戴秋云, 有机化学, 2010, 30,1517.)
	(e) Chi, Y-S.; Zhang,H. -B.; Ni,S. -J.; Huang,W. -L. Chin. J. Org. Chem. 2008, 28,416 (in Chinese).
	( 迟玉石, 张惠斌, 倪帅健, 黄文龙, 有机化学, 2008, 28,416.)
[2]	(a) Góngora-Benítez, M.; Tulla-Puche, J.; Albericio, F. Chem. Rev. 2014, 114,901. doi: 10.1021/cr400031z
	(b) Cemazar, M.; Kwon, S.; Mahatmanto, T.; Ravipati,A. S.; Craik,D. J. Curr. Top. Med. Chem. 2012, 12,1534. doi: 10.2174/156802612802652484
	(c) 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
	(d) Sun,S. -S.; Chen, J.; Zhao, R.; Bierer, D.; Wang, J.; Fang,G. -M.; Li,Y. -M. Tetrahedron Lett. 2019, 60,1197.
	(e) Pan, X.; Li, Z.; Huang, X.; Huang, G.; Gao, S.; Shen, H.; Liu, L.; Lei, J.; Yan, N. Science 2019, 363,1309. doi: 10.1126/science.aaw2999
	(f) Lin King, J.V.; Emrick, J.J.; Kelly, M.J.S.; Herzig, V.; King, G.F.; Medzihradszky, K.F.; Julius, D. Cell 2019, 178,1362. doi: 10.1016/j.cell.2019.07.014
	(g) Guo,X. -Q.; Liang, J.; Li, Y.; Zhang, Y.; Huang, D.; Tian, C. Chin. Chem. Lett. 2018, 29,1139. doi: 10.1016/j.cclet.2018.05.005
	(h) Sun, D.; Liu, S.; Li, S.; Zhang, M.; Yang, F.; Wen, M.; Shi, P.; Wang, T.; Pan, M.; Chang, S.; Zhang, X.; Zhang, L.; Tian, C.; Liu, L. eLife 2020, 9,e57096. doi: 10.7554/eLife.57096
	(i) 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
	(j) Song, H.; Liu, C.; Wu, Y.; Hu, H.; Yan, F. Acta Chim. Sinica 2018, 76,95 (in Chinese). doi: 10.6023/A17100473
[13]	(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
	(b) Qi,Y. -K.; Tang, S.; Huang,Y. -C.; Pan, M.; Zheng,J. -S.; Liu, L. Org. Biomol. Chem. 2016, 14,4194. doi: 10.1039/C6OB00450D
	(c) Qi,Y. -K.; He,Q. -Q.; Ai,H. -S.; Guo, J.; Li,J. -B. Chem. Commun. 2017, 53,4148. doi: 10.1039/C7CC01721A
	(d) Qi,Y. -K.; He,Q. -Q.; Ai,H. -S.; Li,J. -B.; Zheng,J. -S. Synlett 2017, 28,1907. doi: 10.1055/s-0036-1590794
	(e) 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
	(f) Qi,Y. -K.; Ai,H. -S.; Li,Y. -M.; Yan, B. Front. Chem. 2018, 6,19. doi: 10.3389/fchem.2018.00019
[14]	(a) Li, Z.; Zhang, B.; Zuo, C.; Liu, L. Chin. J. Org. Chem. 2018, 38,2412 (in Chinese). doi: 10.6023/cjoc201804014
	( 黎子琛, 张宝昌, 左冲, 刘磊, 有机化学, 2018, 38,2412.)
	(b) Qi,Y. -K.; Si,Y. -Y.; Du,S. -S.; Liang, J.; Wang,K. W.; Zheng,J. -S. Sci. China: Chem. 2019, 62,299. doi: 10.1007/s11426-018-9401-8
	(c) Zhang, B.; Deng, Q.; Zuo, C.; Yan, B.; Zuo, C.; Cao,X. -X.; Zhu,T. F.; Zheng,J. -S.; Liu, L. Angew. Chem.,Int. Ed. 2019, 58,12231. doi: 10.1002/anie.v58.35
	(d) 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
	(e) Zhang, B.; Li, Y.; Shi, W.; Wang, T.; Zhang, F.; Liu, L. Chem. Res. Chin. Univ. 2020, 36,733. doi: 10.1007/s40242-020-0150-y
	(f) Tang, S.; Zheng, J.; Yang, K.; Liu, L. Acta Chim. Sinica 2012, 70,1471 (in Chinese). doi: 10.6023/A12040166
	( 唐姗, 郑基深, 杨可, 刘磊, 化学学报, 2012, 70,1471.)
	(g) 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
[2]	( 宋慧, 刘超, 吴仪君, 胡宏岗, 阎芳, 化学学报, 2018, 76,95.)
[3]	(a) Xu, X.; Xu, Q.; Chen, F.; Shi, J.; Liu, Y.; Chu, Y.; Wan, S.; Jiang, T.; Yu, R. RSC Adv. 2019, 9,668. doi: 10.1039/C8RA06103C
	(b) Zheng, Y.; Zhai, L.; Zhao, Y.; Wu, C. J. Am. Chem. Soc. 2015, 137,15094. doi: 10.1021/jacs.5b10779
	(c) Chen, C.; Gao, S.; Qu, Q.; Mi, P.; Tao, A.; Li,Y. -M. Chin. Chem. Lett. 2018, 29,1135. doi: 10.1016/j.cclet.2018.01.005
	(d) Liu, J.; Dong, S. Chin. Chem. Lett. 2018, 29,1131. doi: 10.1016/j.cclet.2018.05.014
	(e) Zhao, R.; Shi, P.; Chen, J.; Sun, S.; Chen, J.; Cui, J.; Wu, F.; Fang, G.; Tian, C.; Shi, J.; Bierer, D.; Liu, L.; Li,Y. -M. Chem. Sci. 2020, 11,7927. doi: 10.1039/D0SC02374D
	(f) Ge, W.; Chen, J.; Zhang, Y.; Zong, L.; Zhang, M.; Dong, J. Chin. J. Org. Chem. 2017, 37,2409 (in Chinese). doi: 10.6023/cjoc201704020
	( 葛巍巍, 陈静, 张也, 宗良, 张鸣, 董俊军, 有机化学, 2017, 37,2409.)
[4]	Yang, S.; Yang, F.; Wei, N.; Hong, J.; Li, B.; Luo, L.; Rong, M.; Yarov-Yarovoy, V.; Zheng, J.; Wang, K.; Lai, R. Nat. Commun. 2015, 6,8297. doi: 10.1038/ncomms9297
[5]	(a) Chu, Y.; Qiu, P.; Yu, R. Toxins 2020, 12,230. doi: 10.3390/toxins12040230
	(b) Zhu, A.; Aierken, A.; Yao, Z.; Vu, S.; Tian, Y.; Zheng, J.; Yang, S.; Yang, F. Toxicon 2020, 178,41. doi: 10.1016/j.toxicon.2020.02.016
	(c) Du, G.; Tian, Y.; Yao, Z.; Vu, S.; Zheng, J.; Chai, L.; Wang, K.; Yang, S. J. Biol. Chem. 2020, 295,9641. doi: 10.1074/jbc.RA120.013037
	(d) Luo, L.; Wang, Y.; Li, B.; Xu, L.; Kamau,P. M.; Zheng, J.; Yang, F.; Yang, S.; Lai, R. Nat. Commun. 2019, 10,2134. doi: 10.1038/s41467-019-09965-6
	(e) Ombati, R.; Luo, L.; Yang, S.; Lai, R. Toxicon 2018, 154,60. doi: 10.1016/j.toxicon.2018.09.008
	(f) Yu, R.; Liu, H.; Wang, B.; Harvey,P. J.; Wei, N.; Chu, Y. RSC Adv. 2020, 10,2141. doi: 10.1039/C9RA08829F
[6]	Lyu,H. -N.; Wei,N. -N.; Tu,P. -F.; Wang, K.; Jiang, Y. Nat. Prod. Res. 2020, 34,1068. doi: 10.1080/14786419.2018.1548455
[7]	(a) Karas,J. A.; Patil,N. A.; Tailhades, J.; Sani,M. -A.; Scanlon,D. B.; Forbes,B. E.; Gardiner, J.; Separovic, F.; Wade,J. D.; Hossain,M. A. Angew. Chem.,Int. Ed. 2016, 55,14743. doi: 10.1002/anie.v55.47
	(b) Tang, S.; Si,Y. -Y.; Wang,Z. -P.; Mei,K. -R.; Chen, X.; Cheng,J. -Y.; Zheng,J. -S.; Liu, L. Angew. Chem.,Int. Ed. 2015, 54,5713. doi: 10.1002/anie.201500051
[8]	(a) Qu, Q.; Gao, S.; Li,Y. -M. J. Pept. Sci. 2018, 24,e3112. doi: 10.1002/psc.v24.8-9
	(b) Muttenthaler, M.; Nevin,S. T.; Grishin,A. A.; Ngo,S. T.; Choy,P. T.; Daly,N. L.; Hu,S. -H.; Armishaw,C. J.; Wang,C. -I.A.; Lewis,R. J.; Martin,J. L.; Noakes,P. G.; Craik,D. J.; Adams,D. J.; Alewood,P. F. J. Am. Chem. Soc. 2010, 132,3514. doi: 10.1021/ja910602h
	(c) Lan, H.; Wu, K.; Zheng, Y.; Pan, M.; Huang,Y. -C.; Gao, S.; Zheng,Q. -Y.; Zheng,J. -S.; Li,Y. -M.; Xiao, B.; Liu, L. J. Pept. Sci. 2016, 22,320. doi: 10.1002/psc.2868
	(d) 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.201506225
	(e) Zhou, X.; Zuo, C.; Li, W.; Shi, W.; Zhou, X.; Wang, H.; Chen, S.; Du, J.; Chen, G.; Zhai, W.; Zhao, W.; Wu, Y.; Qi, Y.; Liu, L.; Gao, Y. Angew. Chem.,Int. Ed. 2020, 59,15114. doi: 10.1002/anie.v59.35
[9]	(a) Mochizuki, M.; Tsuda, S.; Tanimura, K.; Nishiuchi, Y. Org. Lett. 2015, 17,2202. doi: 10.1021/acs.orglett.5b00786
	(b) Jordan,J. B.; Poppe, L.; Haniu, M.; Arvedson, T.; Syed, R.; Li, V.; Kohno, H.; Kim, H.; Schnier,P. D.; Harvey,T. S.; Miranda,L. P.; Cheetham, J.; Sasu,B. J. J. Biol. Chem. 2009, 284,24155. doi: 10.1074/jbc.M109.017764
[10]	(a) Dowell, C.; Olivera,B. M.; Garrett,J. E.; Staheli,S. T.; Watkins, M.; Kuryatov, A.; Yoshikami, D.; Lindstrom,J. M.; McIntosh,J. M. J. Neurosci. 2003, 23,8445. doi: 10.1523/JNEUROSCI.23-24-08445.2003
	(b) Luo, S.; Akondi,K. B.; Zhangsun, D.; Wu, Y.; Zhu, X.; Hu, Y.; Christensen, S.; Dowell, C.; Daly,N. L.; Craik,D. J.; Wang,C. -I.A.; Lewis,R. J.; Alewood,P. F.; McIntosh,J. M. J. Biol. Chem. 2010, 285,12355. doi: 10.1074/jbc.M109.079012
	(c) Luo, S.; Christensen, S.; Zhangsun, D.; Wu, Y.; Hu, Y.; Zhu, X.; Chhabra, S.; Norton,R. S.; McIntosh,J. M. PLoS One 2013, 8,e54648. doi: 10.1371/journal.pone.0054648
	(d) Shi, J.; So,L. -Y.; Chen, F.; Liang, J.; Chow,H. -Y.; Wong,K. -Y.; Wan, S.; Jiang, T.; Yu, R. J. Pept. Sci. 2018, 24,e3087. doi: 10.1002/psc.v24.6
	(e) Wu, Y.; Wu, X.; Yu, J.; Zhu, X.; Zhangsun, D.; Luo, S. Molecules 2014, 19,966. doi: 10.3390/molecules19010966

蜈蚣毒素多肽RhTx的高效化学合成及复性折叠研究

Efficient Synthesis and Oxidative Folding Studies of Centipede Toxin RhTx

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[1]	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.
[2]	LI Xue-Qiang, WEI Chuan-Wan, LIU Xiao-Fang, LIU You-Nian. Synthesis of Ferrocenoyl-peptide and Its Inhibition for β-Amyloid Peptide [J]. Chin. J. Org. Chem., 2010, 30(10): 1492-1496.
[3]	WU Qiao-Ling, LIU Zhu-Guo, FU Chao, LIN Yuan-Bin, DAI Qiu-Yun. A Mimetic Peptide with Two Pairs of Concentrated Disulfide Bridges [J]. Chin. J. Org. Chem., 2010, 30(10): 1517-1520.
[4]	YANG Ming,WANG Wei-Guo,LI Pei-Hua,ZHANG Jun,SHEN Shu-Bao*. Solid Phase Peptide Coupling and Its Kinetics under Microwave Irradiation [J]. Chin. J. Org. Chem., 2008, 28(05): 851-856.
[5]	CHI Yu-Shi,ZHANG Hui-Bin*,NI Shuai-Jian,HUANG Wen-Long. Solid Phase Synthesis of Cyclopeptides of Oxytocin and Lysipressin under Microwave Irradiation [J]. Chin. J. Org. Chem., 2008, 28(03): 416-421.
[6]	HUANG Xiao-Yi, WANG Tao, XIA Chuan-Qin, YU Xiao-Qi, XIE Ru-Gang. Synthesis of Novel Disulfide Bond-Bearing Cyclopeptides [J]. Chinese Journal of Organic Chemistry, 2004, 24(12): 1629-1632.
[7]	Jiang Hui;Zhong Mingnai;Chen Jisheng;Miao Zhenwei. The advances in the synthesis of multiple disulfide bond-containing peptides [J]. Chin. J. Org. Chem., 1999, 19(3): 214-223.
[8]	Wang Liangyou;Pan Heping;Chen Zhengying. Methods of disulfide formation in peptide synthesis [J]. Chin. J. Org. Chem., 1998, 18(6): 576-580.