靶向酸敏感离子通道的毒素肽: 镇痛机制与生物合成开发

doi:10.6023/A25040105

化学学报 ›› 2025, Vol. 83 ›› Issue (7): 755-772.DOI: 10.6023/A25040105 上一篇下一篇

综述

靶向酸敏感离子通道的毒素肽: 镇痛机制与生物合成开发

李海婷^a^,^b, 吴小余^a^,^*(), 曹春阳^b^,^*()

^a 上海大学理学院化学系上海 200444
^b 中国科学院上海有机化学研究所生命过程小分子调控全国重点实验室上海 200032

投稿日期:2025-04-03 发布日期:2025-07-28

作者简介:

李海婷, 女, 上海大学和中科院上海有机化学研究所2022级联合培养有机化学专业硕士研究生, 主要研究方向为靶向离子通道的毒素多肽的生物合成和应用.

吴小余, 男, 上海大学化学系教授, 博士生导师, 2000~2005年于中科院上海有机化学研究所攻读博士, 2006~2008年于新加坡国立大学进行博士后研究, 2008年进入上海大学工作至今, 主要研究方向为不对称催化和医药中间体合成工艺开发.

曹春阳, 男, 1998~2001年于中科院上海有机化学研究所攻读博士, 2001~2005年在约翰霍普金斯大学医学院分子药理系从事博士后研究, 2005~2006年转至美国Salk生物研究院结构生物学中心从事助理研究员, 2006年至今为中国科学院上海有机化学研究所“百人计划”研究员, 上海市“浦江计划”获得者, 主要研究方向为以NMR技术为主导, 结合蛋白质晶体学, 开展与肿瘤发生与发展、病毒感染相关的蛋白质与核酸结构与功能分子机制研究、天然产物活性分子筛选与药物分子设计.

基金资助:
中国科学院战略性先导科技专项(XDB1060000)

Targeting Acid-Sensing Ion Channels with Toxin Peptides: Analgesic Mechanisms and Biosynthesis Development

Haiting Li^a^,^b, Xiaoyu Wu^a^,^*(), Chunyang Cao^b^,^*()

^a Department of Chemistry, College of Science, Shanghai University, Shanghai 200444, China
^b State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China

Received:2025-04-03 Published:2025-07-28
Contact: *E-mail: wuxy@shu.edu.cn; ccao@mail.sioc.ac.cn;E-mail: ccao@mail.sioc.ac.cn
Supported by:
Strategic Priority Research Program of the Chinese Academy of Sciences(XDB1060000)

文章分享

摘要/Abstract

酸敏感离子通道(ASIC)在酸诱导的疼痛信号传导中发挥关键作用, 其亚型特异性分布为开发精准镇痛药物提供了独特靶点, 例如ASIC1a主要参与中枢敏化过程, ASIC3在外周炎性痛中起核心调控作用. 传统镇痛药物因存在中枢副作用和靶点选择性不足等局限制约了临床应用, 而天然毒素肽如PcTx1、Mambalgin和APETx2通过特异性结合ASIC胞外结构域并精确调控通道门控特性, 可在纳摩尔级浓度水平实现高效镇痛且无成瘾性. 本文系统阐述了ASIC的分子结构和门控机制, 深入分析了代表性毒素肽的作用模式, 继而梳理了毒素肽的生物合成及成药性优化策略, 涵盖原核与真核表达系统的应用优化、化学修饰技术以及基因工程改造方法, 最后探讨了毒素肽药物在临床转化过程中面临的挑战与可能的解决方案. 随着多学科的发展和交叉应用, 毒素肽药物有望突破传统镇痛治疗瓶颈. 本文为基于离子通道靶点的创新镇痛剂研发提供了多维度的技术路线与理论支撑.

关键词: 酸敏感离子通道(ASIC), 毒素肽, 镇痛药物, 生物合成

Acid-sensing ion channels (ASICs), as proton-gated cation channels, play critical roles in acidosis-evoked pain signaling through their subtype-specific contributions to nociceptive pathways. ASIC1a predominantly drives central sensitization in neuropathic pain, while ASIC3 mediates peripheral inflammatory and musculoskeletal pain. While conventional analgesics, such as opioids and nonsteroidal anti-inflammatory drugs, are limited by central side effects and poor selectivity, natural toxin peptides demonstrate remarkable therapeutic potential. PcTx1 (from tarantula venom), Mambalgin (snake-derived), and APETx2 (sea anemone toxin) exhibit nanomolar affinity for ASIC extracellular domains, effectively modulating channel gating to achieve potent analgesia without addiction risks. This review systematically elucidates the molecular architecture and gating mechanisms of ASICs, providing in-depth analysis of representative toxin peptides' mechanisms towards ASICs. PcTx1 stabilizes ASIC1a in a desensitized state through acidic pocket engagement, while Mambalgin-1 locks the thumb domain in resting state to inhibit activation. APETx2 is proposed to block ASIC3 via a basic amino acid cluster binding to the site between palm and wrist domains, as suggested by homology modeling. Biosynthetic strategies have advanced significantly, with Escherichia coli serving as a cost-effective platform for rapid production of disulfide-rich peptides through engineered oxidative folding pathways (e.g., the DisCoTune system). Pichia pastoris enables secretory expression with low immunogenicity by post-translational modification systems and α-mating factor signal peptides. For complex modifications, mammalian cells (e.g., Chinese hamster ovary cells) provide precise folding and human-like post-translational processing. Key optimizations include solubility-enhancing tags (MBP, SUMO), affinity tags (poly-His), and chemical modifications like PEGylation to improve the pharmacokinetics of toxin peptides. Finally, the discussion extends to challenges in clinical translation of toxin peptide drugs, including incomplete ASIC subtype structural resolution and off-target effects. AI-driven design (AlphaFold2-predicted models) and stimuli-responsive nanocarriers (lipid-based systems) may address these limitations. With interdisciplinary advancements and cross-application of technologies, toxin peptides demonstrate promising potential to overcome limitations of conventional analgesic therapies.

Key words: acid-sensing ion channel (ASIC), toxin peptide, analgesics, biosynthesis

引用此文

李海婷, 吴小余, 曹春阳. 靶向酸敏感离子通道的毒素肽: 镇痛机制与生物合成开发[J]. 化学学报, 2025, 83(7): 755-772.

Haiting Li, Xiaoyu Wu, Chunyang Cao. Targeting Acid-Sensing Ion Channels with Toxin Peptides: Analgesic Mechanisms and Biosynthesis Development[J]. Acta Chimica Sinica, 2025, 83(7): 755-772.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

图/表 9

名称	来源	用药方式	作用靶点/机制	主要适应症	临床状态	备注
Cobratide (克痛宁)	中华眼镜蛇 (Naja atra)	静脉注射/口服	烟碱型乙酰胆碱受体阻断剂	慢性关节痛、坐骨神经痛、神经性头痛	已上市	国药准字H53022101^[27]
Ziconotide (Prialt®)	Conus magus	鞘内注射	Cav2.2通道阻断剂	严重慢性疼痛	已上市	New Drug Application (NDA): 021060^[28]
μ-TRTX-Hhn1b (Halneuron)	Ornithoctonus hainana	皮下注射	电压门控钠通道 Nav1.7抑制剂	化疗性神经性疼痛	II期临床	ClinicalTrials.gov ID: NCT06848348^[29]
Tetrodotoxin	pufferfish	肌内注射/皮下注射	电压门控钠通道 Nav阻断剂	中度或重度癌症疼痛、化疗性神经性疼痛	Ⅱ/Ⅲ期临床	ClinicalTrials.gov ID: NCT00726011/NCT00725114/NCT01655823^[29]
ACV-1 (a-Vc1.1)	Conus victoriae	皮下注射	GABA_B受体激活剂	糖尿病性神经病变疼痛	II期临床	因缺乏疗效而停止^[30]
Contulakin-G (CGX-1160)	Conus geographus	鞘内注射	神经降压素受体激活剂	神经病理性疼痛	II期临床	因开发商公司破产而停止^[30]
Leconotide (ω-conotoxin CVID)	Conus catus	鞘内注射	Cav2.2通道阻断剂	神经病理性疼痛	Ⅰ/II期临床	因开发商公司破产而停止^[30]
Xen 2174 (c-CTX MrIA)	Conus marmoreus	鞘内注射	作用于去甲肾上腺素转运体	术后疼痛	II b期临床	已停止^[30]

表1. 已上市或处于临床试验的毒素肽药物

Table 1. Toxin-derived peptide drugs approved or under clinical trials

图1. ASIC通道的分子结构 (A)静息状态cASIC1三聚体侧面构象(PDB号: 6vtl); (B)静息状态cASIC1三聚体俯视构象; (C) cASIC1(灰色, PDB号: 6vtl)与hASIC1a(紫色, PDB号: 7cfs)单亚基结构差异对比

Figure 1. Molecular structure of the ASIC channel (A) Lateral conformation of the resting state cASIC1 trimer (PDB ID: 6vtl); (B) Top view conformation of the resting state cASIC1 trimer; (C) Comparison of the structural differences between the single subunit structures of cASIC1 (grey, PDB ID: 6vtl) and hASIC1a (purple, PDB ID: 7cfs)

图2. ASIC通道pH依赖性门控机制

Figure 2. The pH-dependent gating mechanism for ASIC channel

图3. (A)三种代表性毒素肽的氨基酸序列, 各肽二硫键已标出; (B~D)三种代表性毒素肽的结构, 其中青色为α螺旋, 蓝色为β折叠, 褐色为二硫键(PBD号: PcTx1-3s3x, Mamb-5dz5, APETx2-2mub)

Figure 3. (A) Sequences of three representative toxin peptides, with the disulphide bond of each peptide indicated; (B~D) Structures of three representative toxin peptides, with α helices in cyan, β folds in blue and disulphide bonds in brown (PBD ID: PcTx1-3s3x, Mamb-5dz5, APETx2-2mub)

毒素名称	来源生物	靶向ASIC亚型	调节方式	作用特点
APETx2	海葵	ASIC3	抑制	可能与孔阻塞相关, 非pH依赖
Hi1a	蜘蛛	ASIC1a	抑制	PcTx1的串联体, 更强效长效
Mambalgin	曼巴蛇	ASIC1a、1b	抑制	干扰亚基构象转变, pH依赖
MitTx	珊瑚蛇	ASIC1a	激活	稳定通道开放构象, 组成型激活
PcTx1	蜘蛛	ASIC1a	抑制	稳定通道脱敏构象, pH依赖

表2. 靶向ASIC通道的代表性毒素肽

Table 2. Representative toxin peptides targeting ASIC channels

图4. PcTx1与cASIC1结合复合物, 毒素关键作用残基如图标记(PDB号: 3s3x)

Figure 4. The binding complex of PcTx1 with cASIC1, toxin critical acting residues are labelled as in the figure (PDB ID: 3s3x)

图5. Mambalgin与hASIC1a结合复合物, 毒素关键作用残基如图标记(PDB号: 7cft)

Figure 5. The binding complex of Mambalgin with hASIC1a, toxin critical acting residues are labelled as in the figure (PDB ID: 7cft)

图6. 毒素肽的生物合成路线

Figure 6. Biosynthetic route of toxin peptide

图7. 多肽/蛋白PEG化反应

Figure 7. Peptide/protein PEGylation reactions

参考文献 112

[113]	Baconguis I.; Gouaux E. Nature 2012, 489, 400.
[114]	Cristofori-Armstrong B.; Budusan E.; Rash L. D. Proc. Natl. Acad. Sci. 2021, 118, e2021581118.
[115]	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.
[116]	Besson T.; Lingueglia E.; Salinas M. Neuropharmacology 2017, 125, 429.
[117]	Sun D.; Yu Y.; Xue X.; Pan M.; Wen M.; Li S.; Qu Q.; Li X.; Zhang L.; Li X.; Liu L.; Yang M.; Tian C. Cell Discov. 2018, 4, 27.
[118]	Salinas M.; Kessler P.; Douguet D.; Sarraf D.; Tonali N.; Thai R.; Servent D.; Lingueglia E. Neuropharmacology 2021, 185, 108453.
[119]	Blanchard M. G.; Rash L. D.; Kellenberger S. Br. J. Pharmacol. 2012, 165, 2167.
[120]	Deval E.; Noël J.; Gasull X.; Delaunay A.; Alloui A.; Friend V.; Eschalier A.; Lazdunski M.; Lingueglia E. J. Neurosci. 2011, 31, 6059.
[121]	Peigneur S.; Béress L.; Möller C.; Marí F.; Forssmann W.-G.; Tytgat J. FASEB J. 2012, 26, 5141. doi: 10.1096/fj.12-218479 pmid: 22972919
[122]	Rahman T.; Smith E. S. J. Biochem. Biophys. Res. Commun. 2014, 450, 384.
[123]	Bohlen C. J.; Chesler A. T.; Sharif-Naeini R.; Medzihradszky K. F.; Zhou S.; King D.; Sánchez E. E.; Burlingame A. L.; Basbaum A. I.; Julius D. Nature 2011, 479, 410.
[124]	Lynagh T.; Romero-Rojo J. L.; Lund C.; Pless S. A. J. Med. Chem. 2017, 60, 8192.
[125]	Voilley N.; de Weille J.; Mamet J.; Lazdunski M. J. Neurosci. 2001, 21, 8026. pmid: 11588175
[1]	Fan B. F. China Pain Medicine Development Report (2020), Tsinghua University Press, Beijing, 2020, Chapter 1.1 (in Chinese).
	(樊碧发, 中国疼痛医学发展报告(2020), 清华大学出版社, 北京, 2020, 章节1.1.)
[2]	Fürst S.; Zádori Z. S.; Zádor F.; Király K.; Balogh M.; László S. B.; Hutka B.; Mohammadzadeh A.; Calabrese C.; Galambos A. R.; Riba P.; Romualdi P.; Benyhe S.; Timár J.; Schmidhammer H.; Spetea M.; Al-Khrasani M. Molecules 2020, 25, 2473.
[3]	Provisional Drug Overdose Death Counts; The Centers for Disease Control and Prevention, 2025. https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm. (accessed 2025-05-21).
[4]	Bindu S.; Mazumder S.; Bandyopadhyay U. Biochem. Pharmacol. 2020, 180, 114147.
[5]	Waldmann R.; Champigny G.; Bassilana F.; Heurteaux C.; Lazdunski M. Nature 1997, 386, 173.
[6]	Carnally S. M.; Dev H. S.; Stewart A. P.; Barrera N. P.; Van Bemmelen M. X.; Schild L.; Henderson R. M.; Edwardson J. M. Biochem. Biophys. Res. Commun. 2008, 372, 752.
[7]	Jasti J.; Furukawa H.; Gonzales E. B.; Gouaux E. Nature 2007, 449, 316.
[126]	Lin Y.-W.; Min M.-Y.; Lin C.-C.; Chen W.-N.; Wu W.-L.; Yu H.-M.; Chen C.-C. Neuroscience 2008, 151, 544. doi: 10.1016/j.neuroscience.2007.10.020 pmid: 18082972
[127]	Osmakov D. I.; Koshelev S. G.; Andreev Y. A.; Kozlov S. A. Front. Mol. Neurosci. 2017, 10, 282. doi: 10.3389/fnmol.2017.00282 pmid: 28955199
[128]	Zaremba M.; Ruiz-Velasco V. Mol. Pharmacol. 2019, 95, 519.
[129]	Osmakov D. I.; Onoprienko L. V.; Kalinovskii A. P.; Koshelev S. G.; Stepanenko V. N.; Andreev Y. A.; Kozlov S. A. Int. J. Mol. Sci. 2024, 25, 1413.
[130]	Roush G. C.; Ernst M. E.; Kostis J. B.; Yeasmin S.; Sica D. A. J. Hypertens. 2016, 34, 11.
[131]	Dulai J. S.; Smith E. St. J.; Rahman T. Channels 2021, 15, 94.
[132]	Rivera-de-Torre E.; Rimbault C.; Jenkins T. P.; Sørensen C. V.; Damsbo A.; Saez N. J.; Duhoo Y.; Hackney C. M.; Ellgaard L.; Laustsen A. H. Front. Bioeng. Biotechnol. 2021, 9, 811905.
[8]	Lingueglia E.; de Weille J. R.; Bassilana F.; Heurteaux C.; Sakai H.; Waldmann R.; Lazdunski M. J. Biol. Chem. 1997, 272, 29778. doi: 10.1074/jbc.272.47.29778 pmid: 9368048
[9]	Akopian A. N.; Chen C. C.; Ding Y.; Cesare P.; Wood J. N. Neuroreport 2000, 11, 2217. doi: 10.1097/00001756-200007140-00031 pmid: 10923674
[10]	Walder R. Y.; Rasmussen L. A.; Rainier J. D.; Light A. R.; Wemmie J. A.; Sluka K. A. J. Pain 2010, 11, 210.
[11]	De Logu F.; Geppetti P. Handb. Exp. Pharmacol. 2019, 260, 161.
[12]	Schmidtko A.; Lötsch J.; Freynhagen R.; Geisslinger G. Lancet 2010, 375, 1569. doi: 10.1016/S0140-6736(10)60354-6 pmid: 20413151
[13]	Escoubas P.; De Weille J. R.; Lecoq A.; Diochot S.; Waldmann R.; Champigny G.; Moinier D.; Ménez A.; Lazdunski M. J. Biol. Chem. 2000, 275, 25116. doi: 10.1074/jbc.M003643200 pmid: 10829030
[14]	Diochot S.; Baron A.; Salinas M.; Douguet D.; Scarzello S.; Dabert-Gay A.-S.; Debayle D.; Friend V.; Alloui A.; Lazdunski M.; Lingueglia E. Nature 2012, 490, 552.
[133]	Stewart E. J.; Aslund F.; Beckwith J. EMBO J. 1998, 17, 5543. doi: 10.1093/emboj/17.19.5543 pmid: 9755155
[134]	Salinas G.; Pellizza L.; Margenat M.; Fló M.; Fernández C. Biotechnol. J. 2011, 6, 686.
[135]	Baumgarten T.; Ytterberg A. J.; Zubarev R. A.; de Gier J.-W. Appl. Environ. Microbiol. 2018, 84, e00270-18.
[136]	Freudl R. Microb. Cell Fact. 2018, 17, 52.
[137]	Bessette P. H.; Aslund F.; Beckwith J.; Georgiou G. Proc. Natl. Acad. Sci. U. S. A. 1999, 96, 13703.
[138]	Ritz D.; Lim J.; Reynolds C. M.; Poole L. B.; Beckwith J. Science 2001, 294, 158. pmid: 11588261
[139]	Lobstein J.; Emrich C. A.; Jeans C.; Faulkner M.; Riggs P.; Berkmen M. Microb. Cell Fact. 2012, 11, 753.
[140]	Alanen H. I.; Walker K. L.; Lourdes Velez Suberbie M.; Matos C. F. R. O.; Bönisch S.; Freedman R. B.; Keshavarz-Moore E.; Ruddock L. W.; Robinson C. Biochim. Biophys. Acta 2015, 1853, 756. doi: 10.1016/j.bbamcr.2014.12.027 pmid: 25554517
[15]	Diochot S.; Baron A.; Rash L. D.; Deval E.; Escoubas P.; Scarzello S.; Salinas M.; Lazdunski M. EMBO J. 2004, 23, 1516. doi: 10.1038/sj.emboj.7600177 pmid: 15044953
[16]	Izumi M.; Ikeuchi M.; Ji Q.; Tani T. J. Biomed. Sci. 2012, 19, 77.
[17]	Holton C. M.; Strother L. C.; Dripps I.; Pradhan A. A.; Goadsby P. J.; Holland P. R. Br. J. Pharmacol. 2020, 177, 2478.
[18]	Jensen J. E.; Durek T.; Alewood P. F.; Adams D. J.; King G. F.; Rash L. D. Toxicon 2009, 54, 56. doi: 10.1016/j.toxicon.2009.03.014 pmid: 19306891
[19]	Schroeder C. I.; Rash L. D.; Vila-Farrés X.; Rosengren K. J.; Mobli M.; King G. F.; Alewood P. F.; Craik D. J.; Durek T. Angew. Chem. Int. Ed. 2014, 53, 1017.
[20]	Zhang W. J.; Zhang F. J.; Zhao S. F.; Dong Y. X.; Guo K.; Ji S. L. J. Binzhou Med. Univ. 2024, 47, 94 (in Chinese).
	(张文杰, 张发进, 赵仕法, 董玉香, 郭凯, 姬胜利, 滨州医学院学报, 2024, 47, 94.)
[21]	Peng W.; Cheng R.; Liu H.; Liu D. M.; Su X. B. Chin. J. Org. Chem. 2024, 44, 2876 (in Chinese).
[141]	Nguyen V. D.; Hatahet F.; Salo K. E. H.; Enlund E.; Zhang C.; Ruddock L. W. Microb. Cell Fact. 2011, 10, 1. doi: 10.1186/1475-2859-10-1 pmid: 21211066
[142]	Bertelsen A. B.; Hackney C. M.; Bayer C. N.; Kjelgaard L. D.; Rennig M.; Christensen B.; Sørensen E. S.; Safavi-Hemami H.; Wulff T.; Ellgaard L.; Nørholm M. H. H. Microb. Biotechnol. 2021, 14, 2566. doi: 10.1111/1751-7915.13895 pmid: 34405535
[143]	Schlegel S.; Löfblom J.; Lee C.; Hjelm A.; Klepsch M.; Strous M.; Drew D.; Slotboom D. J.; de Gier J.-W. J. Mol. Biol. 2012, 423, 648. doi: 10.1016/j.jmb.2012.07.019 pmid: 22858868
[144]	Zhu L.; Yuan C.; Chen Z.; Wang W.; Huang M. Toxicon 2010, 55, 375.
[145]	Ahmad M.; Hirz M.; Pichler H.; Schwab H. Appl. Microbiol. Biotechnol. 2014, 98, 5301.
[146]	Zhou Q.; Qiu H. J. Pharm. Sci. 2019, 108, 1366.
[147]	Karbalaei M.; Rezaee S. A.; Farsiani H. J. Cell. Physiol. 2020, 235, 5867. doi: 10.1002/jcp.29583 pmid: 32057111
[21]	(彭伟, 程蓉, 刘豪, 刘冬梅, 苏贤斌, 有机化学, 2024, 44, 2876.) doi: 10.6023/cjoc202403015
[22]	Yu G.; Zou S.; Zheng J. S. Chembiochem 2024, 25, e202400674.
[23]	Wang J. Y.; Dong L. Y.; Liu Y. N.; Chen X. T.; Ma Y. N.; Yin H.; Du S. S.; Qi Y. K.; Wang K. W. Chin. J. Org. Chem. 2021, 41, 2800 (in Chinese).
	(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
[24]	Yin H.; Chen X. T.; Fu X. Y.; Ma Y. N.; Xu Y. M.; Zhang T.; Liang S.; Du S. S.; Qi Y. K.; Wang K. W. Acta Chim. Sinica 2022, 80, 444 (in Chinese).
	(尹昊, 陈西同, 付邢言, 马艳楠, 徐以梅, 张特, 梁帅, 杜姗姗, 齐昀坤, 王克威, 化学学报, 2022, 80, 444.) doi: 10.6023/A21120580
[25]	Ma Y. N.; Liu Y. N.; Wang J. Y.; Chen X. T.; Yin H.; Chi Q. N.; Jia S. X.; Du S. S.; Qi Y. K.; Wang K. W. Chin. J. Org. Chem. 2022, 42, 498 (in Chinese).
	(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, 有机化学, 2022, 42, 498.) doi: 10.6023/cjoc202109003
[26]	Ho T. N.; Tran T. H.; Le H. S.; Lewis R. J. Eur. J. Med. Chem. 2025, 282, 117038.
[27]	National Medical Products Administration, Drugs. https://www.nmpa.gov.cn/datasearch/home-index.html#category=yp (accessed 2025-05-21) in Chinese).
	( 国家药品监督管理局, 药品查询. https://www.nmpa.gov.cn/datasearch/home-index.html#category=yp 访问于2025-05-21)
[28]	US Food and Drug Administration. https://www.accessdata.fda.gov/scripts/cder/daf/(accessed 2025-05-21).
[29]	US National Library of Medicine. https://clinicaltrials.gov/(accessed 2025-05-21).
[30]	Bordon K. Cologna C. T.; Fornari-Baldo E. C.; Pinheiro-Júnior E. L.; Cerni F. A.; Amorim F. G.; Anjolette F. A. P.; Cordeiro F. A.; Wiezel G. A.; Cardoso I. A.; Ferreira I. G.; de Oliveira I. S.; Boldrini-França J.; Pucca M. B.; Baldo M. A.; Arantes E. C. Front. Pharmacol. 2020, 11, 1132.
[148]	Jacobs P. P.; Geysens S.; Vervecken W.; Contreras R.; Callewaert N. Nat. Protoc. 2009, 4, 58.
[149]	O’Flaherty R.; Bergin A.; Flampouri E.; Mota L. M.; Obaidi I.; Quigley A.; Xie Y.; Butler M. Biotechnol. Adv. 2020, 43, 107552.
[150]	Yadav D. K.; Yadav N.; Yadav S.; Haque S.; Tuteja N. Arch. Biochem. Biophys. 2016, 612, 57.
[151]	Ki M.-R.; Pack S. P. Appl. Microbiol. Biotechnol. 2020, 104, 2411. doi: 10.1007/s00253-020-10402-8 pmid: 31993706
[152]	Kapust R. B.; Waugh D. S. Protein Sci. 1999, 8, 1668. doi: 10.1110/ps.8.8.1668 pmid: 10452611
[153]	Raran-Kurussi S.; Keefe K.; Waugh D. S. Protein Expression Purif. 2015, 110, 159.
[154]	di Guan C.; Li P.; Riggs P. D.; Inouye H. Gene 1988, 67, 21. pmid: 2843437
[155]	Kaplan W.; Hüsler P.; Klump H.; Erhardt J.; Sluis-Cremer N.; Dirr H. Protein Sci. 1997, 6, 399. pmid: 9041642
[31]	Anangi R.; Rash L. D.; Mobli M.; King G. F. Mar. Drugs 2012, 10, 1605.
[32]	Saez N. J.; Cristofori-Armstrong B.; Anangi R.; King G. F. In Heterologous Gene Expression in E. coli, Vol. 1586, Ed.: Burgess- Brown, N. A., Springer, New York, 2017, p. 155.
[33]	Xu J.; Lei X.; Li A.; Li J.; Li S.; Chen L. Microb. Cell Fact. 2024, 23, 48.
[34]	Yin S. J.; Xiao M.; Xiang Q. L.; Li Y. Y.; Liu K. Y.; Zhao Q. R. J. South-Central Minzu Univ. (Nat. Sci. Ed.) 2023, 42, 313 (in Chinese).
	(尹世金, 肖敏, 向琪琳, 李昱烨, 刘柯驿, 赵倩茹, 中南民族大学学报(自然科学版), 2023, 42, 313.)
[35]	Yan S.; Tang X. C.; Yu D. M.; Wang H. Y.; Meng W. W.; Tang P. P.; Wang X. C. Chin. J. Biotechnol. 2021, 37, 635 (in Chinese).
	(颜帅, 唐小超, 余典梅, 王海燕, 孟雯雯, 唐萍萍, 王贤纯, 生物工程学报, 2021, 37, 635.)
[36]	Long S. R.; Li Z. Y.; Zhou Y. X.; Zhao Q. R.; Li Y.; Zhang X.; Yin S. J. J. Xuzhou Inst. Technol. (Nat. Sci. Ed.) 2021, 36, 86 (in Chinese).
	(龙思如, 李子怡, 周雨璇, 赵倩茹, 李奕, 张旭, 尹世金, 徐州工程学院学报(自然科学版), 2021, 36, 86.)
[37]	Mastropietro G.; Aw R.; Polizzi K. M. Methods Enzymol. 2021, 660, 53. doi: 10.1016/bs.mie.2021.07.004 pmid: 34742398
[38]	Anangi R.; Chen C. C.; Lin Y. W.; Cheng Y. R.; Cheng C. H.; Chen Y. C.; Chu Y. P.; Chuang W. J. Toxicon 2010, 56, 1388.
[156]	Lim K.; Ho J. X.; Keeling K.; Gilliland G. L.; Ji X.; Rüker F.; Carter D. C. Protein Sci. 1994, 3, 2233. pmid: 7538846
[157]	Smith M.; Turki-Judeh W.; Courey A. J. Biomolecules 2012, 2, 331.
[158]	Krumova P.; Meulmeester E.; Garrido M.; Tirard M.; Hsiao H.-H.; Bossis G.; Urlaub H.; Zweckstetter M.; Kügler S.; Melchior F.; Bähr M.; Weishaupt J. H. J. Cell. Biol. 2011, 194, 49.
[159]	Melchior F. Annu. Rev. Cell Dev. Biol. 2000, 16, 591. pmid: 11031248
[160]	Kuo D.; Nie M.; Courey A. J. Methods Mol. Biol. 2014, 1177, 71.
[161]	Dashivets T.; Wood N.; Hergersberg C.; Buchner J.; Haslbeck M. Chembiochem 2009, 10, 869. doi: 10.1002/cbic.200800697 pmid: 19235820
[162]	Bernier S. C.; Cantin L.; Salesse C. Protein Expression Purif. 2018, 152, 92.
[163]	Hopp T. P.; Prickett K. S.; Price V. L.; Libby R. T.; March C. J.; Pat Cerretti D.; Urdal D. L.; Conlon P. J. Nat. Biotechnol. 1988, 6, 1204.
[164]	Kane J. F. Curr. Opin. Biotechnol. 1995, 6, 494.
[165]	Liu B.; Kong Q.; Zhang D.; Yan L. 3 Biotech 2018, 8, 210.
[166]	Baeshen M. N.; Al-Hejin A. M.; Bora R. S.; Ahmed M. M. M.; Ramadan H. A. I.; Saini K. S.; Baeshen N. A.; Redwan E. M. J. Microbiol. Biotechnol. 2015, 25, 953.
[167]	Chen P.-Y.; Yi Y.-C.; Wang H.-C.; Ng I.-S. Appl. Biochem. Biotechnol. 2023, 195, 4524.
[168]	Tegel H.; Tourle S.; Ottosson J.; Persson A. Protein Expression Purif. 2010, 69, 159.
[169]	Ouephanit C.; Boonvitthya N.; Bozonnet S.; Chulalaksananukul W. Molecules 2019, 24, 3515.
[170]	Fahnert B.; Lilie H.; Neubauer P. Adv. Biochem. Eng. Biotechnol. 2004, 89, 93.
[171]	Khattar S. K.; Gulati P.; Kundu P. K.; Singh V.; Bughani U.; Bajpai M.; Saini K. S. Protein Pept. Lett. 2007, 14, 756. pmid: 17979814
[39]	Jiang L. P.; Zhang J.; Li X. Y.; Tang Y. Q. J. Pathog. Biol. 2016, 11, 603 (in Chinese).
	(蒋立平, 章洁, 李先耀, 唐雅琴, 中国病原生物学杂志, 2016, 11, 603.)
[40]	Zhu W. H.; Zhang W.; Xu J. J.; Li Y.; Zhang H.; Wang H. Y. Biotechnol. Bull. 2017, 27, 239 (in Chinese).
	(朱文赫, 张巍, 徐俊杰, 李妍, 张红, 王会岩, 生物技术, 2017, 27, 239.)
[41]	Escoubas P.; Bernard C.; Lambeau G.; Lazdunski M.; Darbon H. Protein Sci. 2003, 12, 1332. pmid: 12824480
[42]	Tihanyi B.; Nyitray L. Drug Discovery Today: Technol. 2020, 38, 25.
[43]	Schuhmacher L.-N.; Srivats S.; Smith E. S. J. Mol. Pharmacol. 2015, 87, 561.
[44]	Verkest C.; Salinas M.; Diochot S.; Deval E.; Lingueglia E.; Baron A. Toxins 2022, 14, 709.
[45]	Rook M. L.; Williamson A.; Lueck J. D.; Musgaard M.; Maclean D. M. eLife 2020, 9, e51111.
[46]	Rook M. L.; Ananchenko A.; Musgaard M.; MacLean D. M. Front. Cell. Neurosci. 2021, 15, 761813.
[47]	Yoder N.; Gouaux E. eLife 2020, 9, e56527.
[172]	Ma Y.; Lee C.-J.; Park J.-S. Antibiotics (Basel, Switz.) 2020, 9, 541.
[173]	Yang Q.; Xu J.; Li M.; Lei X.; An L. Biotechnol. Lett. 2003, 25, 607.
[174]	Lawrence P. B.; Price J. L. Curr. Opin. Chem. Biol. 2016, 34, 88. doi: S1367-5931(16)30103-X pmid: 27580482
[175]	Norton R. S. Expert Opin. Drug Discovery 2017, 12, 611.
[176]	Pinheiro-Junior E. L.; Boldrini-França J.; Takeda A. A. S.; Costa T. R.; Peigneur S.; Cardoso I. A.; Oliveira I. S. de; Sampaio S. V.; de Mattos Fontes M. R.; Tytgat J.; Arantes E. C. Int. J. Biol. Macromol. 2021, 190, 564. doi: 10.1016/j.ijbiomac.2021.09.004 pmid: 34506860
[177]	Tanner M. R.; Tajhya R. B.; Huq R.; Gehrmann E. J.; Rodarte K. E.; Atik M. A.; Norton R. S.; Pennington M. W.; Beeton C. Clin. Immunol. 2017, 180, 45. doi: S1521-6616(16)30620-9 pmid: 28389388
[178]	Wender P. A.; Mitchell D. J.; Pattabiraman K.; Pelkey E. T.; Steinman L.; Rothbard J. B. Proc. Natl. Acad. Sci. 2000, 97, 13003.
[48]	Wu Y.; Chen Z.; Sigworth F. J.; Canessa C. M. Elife 2021, 10, e67115.
[49]	Yoder N.; Yoshioka C.; Gouaux E. Nature 2018, 555, 397.
[50]	Baconguis I.; Bohlen C. J.; Goehring A.; Julius D.; Gouaux E. Cell 2014, 156, 717. doi: 10.1016/j.cell.2014.01.011 pmid: 24507937
[51]	Yoder N.; Gouaux E. PLoS One 2018, 13, e0202134.
[52]	Gonzales E. B.; Kawate T.; Gouaux E. Nature 2009, 460, 599.
[53]	Li T.; Yang Y.; Canessa C. M. J. Biol. Chem. 2010, 285, 31285.
[54]	Wu Y.; Chen Z.; Canessa C. M. Elife 2019, 8, e45851.
[55]	Delaunay A.; Gasull X.; Salinas M.; Noël J.; Friend V.; Lingueglia E.; Deval E. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 13124.
[56]	Springauf A.; Bresenitz P.; Gründer S. J. Biol. Chem. 2011, 286, 24374. doi: 10.1074/jbc.M111.230797 pmid: 21576243
[179]	Teesalu T.; Sugahara K. N.; Kotamraju V. R.; Ruoslahti E. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 16157.
[180]	Otvos L.; Wade J. D. Front. Chem. 2014, 2, 62.
[181]	Egleton R. D.; Davis T. P. NeuroRx 2005, 2, 44.
[182]	Egleton R. D.; Mitchell S. A.; Huber J. D.; Palian M. M.; Polt R.; Davis T. P. J. Pharmacol. Exp. Ther. 2001, 299, 967. pmid: 11714884
[183]	Desino K. E.; Pignatello R.; Guccione S.; Basile L.; Ansar S.; Michaelis M. L.; Ramsay R. R.; Audus K. L. Biochem. Pharmacol. 2009, 78, 1412. doi: 10.1016/j.bcp.2009.07.027 pmid: 19679106
[184]	Pignatello R.; Puleo A.; Guccione S.; Raciti G.; Acquaviva R.; Campisi A.; Ventura C. A.; Puglisi G. Eur. J. Med. Chem. 2005, 40, 1074. pmid: 16126309
[185]	Wang J.; Hogenkamp D. J.; Tran M.; Li W.-Y.; Yoshimura R. F.; Johnstone T. B. C.; Shen W.-C.; Gee K. W. J. Drug Targeting 2006, 14, 127.
[57]	Sluka K. A.; Winter O. C.; Wemmie J. A. Curr. Opin. Drug Discov. Devel. 2009, 12, 693.
[58]	Grifoni S. C.; Jernigan N. L.; Hamilton G.; Drummond H. A. Microvasc. Res. 2008, 75, 202. doi: 10.1016/j.mvr.2007.08.003 pmid: 17936312
[59]	Atmani K.; Meleine M.; Langlois L.; Coëffier M.; Brumovsky P.; Leroi A.-M.; Gourcerol G. Front. Pain Res. (Lausanne) 2023, 4, 1083514.
[60]	Page A. J.; Brierley S. M.; Martin C. M.; Price M. P.; Symonds E.; Butler R.; Wemmie J. A.; Blackshaw L. A. Gut 2005, 54, 1408. doi: 10.1136/gut.2005.071084 pmid: 15987792
[61]	Hughes P. A.; Brierley S. M.; Young R. L.; Blackshaw L. A. J. Comp. Neurol. 2007, 500, 863.
[62]	Wu J.; Xu Y.; Jiang Y.-Q.; Xu J.; Hu Y.; Zha X. Mol. Brain. 2016, 9, 4.
[63]	Wemmie J. A.; Askwith C. C.; Lamani E.; Cassell M. D.; Freeman J. H.; Welsh M. J. J. Neurosci. 2003, 23, 5496. pmid: 12843249
[186]	Varamini P.; Toth I. Front. Pharmacol. 2013, 4, 155. doi: 10.3389/fphar.2013.00155 pmid: 24379782
[187]	Tripathi A.; Varadarajan R. Curr. Opin. Struct. Biol. 2014, 24, 63.
[188]	Crameri A.; Raillard S. A.; Bermudez E.; Stemmer W. P. Nature 1998, 391, 288.
[189]	Shcherbatko A.; Rossi A.; Foletti D.; Zhu G.; Bogin O.; Galindo Casas M.; Rickert M.; Hasa-Moreno A.; Bartsevich V.; Crameri A.; Steiner A. R.; Henningsen R.; Gill A.; Pons J.; Shelton D. L.; Rajpal A.; Strop P. J. Biol. Chem. 2016, 291, 13974. doi: 10.1074/jbc.M116.725978 pmid: 27129258
[190]	Muntoni E.; Marini E.; Ahmadi N.; Milla P.; Ghè C.; Bargoni A.; Capucchio M. T.; Biasibetti E.; Battaglia L. Acta Diabetol. 2019, 56, 1283.
[191]	Griesser J.; Hetényi G.; Moser M.; Demarne F.; Jannin V.; Bernkop-Schnürch A. Int. J. Pharm. 2017, 520, 267.
[64]	Lin S.-H.; Sun W.-H.; Chen C.-C. Neuropharmacology 2015, 94, 99.
[65]	Han D.-S.; Lee C.-H.; Shieh Y.-D.; Chang C.-T.; Li M.-H.; Chu Y.-C.; Wang J.-L.; Chang K.-V.; Lin S.-H.; Chen C.-C. Pain 2022, 163, e622.
[66]	Gregory N. S.; Gautam M.; Benson C. J.; Sluka K. A. Neuroscience 2018, 386, 166.
[67]	Homma Y.; Nomiya A.; Tagaya M.; Oyama T.; Takagaki K.; Nishimatsu H.; Igawa Y. J. Urol. 2013, 190, 1925.
[68]	Bässler E.-L.; Ngo-Anh T. J.; Geisler H.-S.; Ruppersberg J. P.; Gründer S. J. Biol. Chem. 2001, 276, 33782. doi: 10.1074/jbc.M104030200 pmid: 11448963
[69]	Jiang Q.; Zha X.-M.; Chu X.-P. Int. J. Physiol. Pathophysiol. Pharmacol. 2012, 4, 84.
[70]	Askwith C. C.; Wemmie J. A.; Price M. P.; Rokhlina T.; Welsh M. J. J. Biol. Chem. 2004, 279, 18296.
[192]	Fonte P.; Araújo F.; Reis S.; Sarmento B. J. Diabetes Sci. Technol. 2013, 7, 520.
[193]	Haddadzadegan S.; Dorkoosh F.; Bernkop-Schnürch A. Adv. Drug Delivery Rev. 2022, 182, 114097.
[194]	Hintzen F.; Perera G.; Hauptstein S.; Müller C.; Laffleur F.; Bernkop-Schnürch A. Int. J. Pharm. 2014, 472, 20.
[195]	Scannell J. W.; Blanckley A.; Boldon H.; Warrington B. Nat. Rev. Drug Discov. 2012, 11, 191. doi: 10.1038/nrd3681 pmid: 22378269
[196]	Xu Y.-Y.; Ma X.-H.; Zhang S.-J. Int. J. Clin. Pharm. Th. 2016, 54, 129.
[197]	Wei J.; Zhu M.; Zhang Z.; Jia Z.; He X.; Wan Y.; Wang S.; Xiu D.; Tang Y.; Li J.; Xu J.; Heng Q. Chinese Med. J-peking. 2010, 123, 589.
[198]	Markland F. S.; Swenson S. Toxins (Basel) 2010, 2, 793.
[199]	Shah A. R.; Scher L. IDrugs 2007, 10, 329.
[71]	Jiang N.; Wu J.; Leng T.; Yang T.; Zhou Y.; Jiang Q.; Wang B.; Hu Y.; Ji Y.-H.; Simon R. P.; Chu X.-P.; Xiong Z.-G.; Zha X.-M. J. Cereb. Blood Flow Metab. 2017, 37, 528.
[72]	Fila M.; Sassi A.; Brideau G.; Cheval L.; Morla L.; Houillier P.; Walter C.; Gennaoui M.; Collignon L.; Keck M.; Planelles G.; Bakouh N.; Peuchmaur M.; Deschênes G.; Anegon I.; Remy S.; Vogt B.; Crambert G.; Doucet A. JCI Insight 2021, 6, e148588.
[73]	Deval E.; Salinas M.; Baron A.; Lingueglia E.; Lazdunski M. J. Biol. Chem. 2004, 279, 19531.
[74]	Montaño J. A.; Calavia M. G.; García-Suárez O.; Suarez-Quintanilla J. A.; Gálvez A.; Pérez-Piñera P.; Cobo J.; Vega J. A. Neurosci. Lett. 2009, 463, 114. doi: 10.1016/j.neulet.2009.07.073 pmid: 19646506
[75]	Cabo R.; Gálvez M. A.; San José I.; Laurà R.; López-Muñiz A.; García-Suárez O.; Cobo T.; Insausti R.; Vega J. A. Neurosci. Lett. 2012, 516, 197. pmid: 22708125
[200]	Iannone L. F.; Nassini R.; Patacchini R.; Geppetti P.; De Logu F. Temperature (Austin) 2023, 10, 50. doi: 10.1080/23328940.2022.2075218 pmid: 37187829
[201]	Dong C.-R.; Zhang W.-J.; Luo H.-L. Biomed. Pharmacother. 2022, 150, 113029.
[76]	Sluka K. A.; Gregory N. S. Neuropharmacology 2015, 94, 58.
[77]	Lin S.-H.; Cheng Y.-R.; Banks R. W.; Min M.-Y.; Bewick G. S.; Chen C.-C. Nat. Commun. 2016, 7, 11460.
[78]	Peng Z.; Li W.-G.; Huang C.; Jiang Y.-M.; Wang X.; Zhu M. X.; Cheng X.; Xu T.-L. Cell Rep. 2015, 13, 387.
[79]	Lee C.-H.; Lin J.-H.; Lin S.-H.; Chang C.-T.; Wu Y.-W.; Bewick G.; Banks R. W.; Gründer S.; Hochgeschwender U.; Chen C.-C. Sci. Adv. 2025, 11, eabc5219.
[80]	Cheng Y.-R.; Jiang B.-Y.; Chen C.-C. J. Biomed. Sci. 2018, 25, 46.
[81]	Hung C.-H.; Chin Y.; Fong Y.-O.; Lee C.-H.; Han D.-S.; Lin J.-H.; Sun W.-H.; Chen C.-C. Pharmacol. Ther. 2023, 247, 108444.
[82]	Donier E.; Rugiero F.; Jacob C.; Wood J. N. Eur. J. Neurosci. 2008, 28, 74.
[83]	Hoshikawa M.; Kato A.; Hojo H.; Shibata Y.; Kumamoto N.; Watanabe M.; Ugawa S. Neurosci. Lett. 2017, 651, 57. doi: S0304-3940(17)30373-7 pmid: 28461138
[84]	Deval E.; Noël J.; Lay N.; Alloui A.; Diochot S.; Friend V.; Jodar M.; Lazdunski M.; Lingueglia E. EMBO J. 2008, 27, 3047.
[85]	Gu Q.; Lee L.-Y. Pharmaceuticals (Basel) 2010, 3, 1411.
[86]	Kang Y. Q.; Chen K.; He X. H.; Yin H.; Mao L. W.; Lu Z. N.; Xiao Z. M. Neural Inj. Funct. Reconstr. 2016, 11, 5 (in Chinese).
	(康玉琪, 陈康, 何小华, 尹皓, 毛立武, 卢祖能, 肖哲曼, 神经损伤与功能重建, 2016, 11, 5.)
[87]	Diochot S.; Alloui A.; Rodrigues P.; Dauvois M.; Friend V.; Aissouni Y.; Eschalier A.; Lingueglia E.; Baron A. Pain 2016, 157, 552. doi: 10.1097/j.pain.0000000000000397 pmid: 26492527
[88]	Matricon J.; Gelot A.; Etienne M.; Lazdunski M.; Muller E.; Ardid D. Eur. J. Pain 2011, 15, 335. doi: 10.1016/j.ejpain.2010.08.005 pmid: 20888277
[89]	Chang C.-T.; Fong S. W.; Lee C.-H.; Chuang Y.-C.; Lin S.-H.; Chen C.-C. Front. Neurosci. 2019, 13, 1247.
[90]	Nagakura Y.; Oe T.; Aoki T.; Matsuoka N. Pain 2009, 146, 26.
[91]	Sugimura N.; Ikeuchi M.; Izumi M.; Kawano T.; Aso K.; Kato T.; Ushida T.; Yokoyama M.; Tani T. Eur. J. Pain 2015, 19, 629. doi: 10.1002/ejp.584 pmid: 25158678
[92]	Xu C.; Gu Y.; Shi Y. T.; Wang G. X.; Niu X. P. J. Shenyang Med. Coll. 2023, 25, 19 (in Chinese).
	(许草, 顾勇, 石亚婷, 汪桂祥, 牛小平, 沈阳医学院学报, 2023, 25, 19.)
[93]	Chassagnon I. R.; McCarthy C. A.; Chin Y. K.-Y.; Pineda S. S.; Keramidas A.; Mobli M.; Pham V.; De Silva T. M.; Lynch J. W.; Widdop R. E.; Rash L. D.; King G. F. Proc. Natl. Acad. Sci. 2017, 114, 3750.
[94]	Budusan E.; Payne C. D.; Gonzalez T. I.; Obergrussberger A.; Becker N.; Clark R. J.; Johan Rosengren K.; Rash L. D.; Cristofori-Armstrong B. Biochem. Pharmacol. 2024, 228, 116175.
[95]	Osmakov D. I.; Kozlov S. A.; Andreev Y. A.; Koshelev S. G.; Sanamyan N. P.; Sanamyan K. E.; Dyachenko I. A.; Bondarenko D. A.; Murashev A. N.; Mineev K. S.; Arseniev A. S.; Grishin E. V. J. Biol. Chem. 2013, 288, 23116. doi: 10.1074/jbc.M113.485516 pmid: 23801332
[96]	Kozlov S. A.; Osmakov D. I.; Andreev I. A.; Koshelev S. G.; Gladkikh I. N.; Monastyrnaia M. M.; Kozlovskaia E. P.; Grishin E. V. Bioorg. Khim. 2012, 38, 653.
[97]	Possani L. D.; Merino E.; Corona M.; Bolivar F.; Becerril B. Biochimie 2000, 82, 861. doi: 10.1016/s0300-9084(00)01167-6 pmid: 11086216
[98]	Pallaghy P. K.; Nielsen K. J.; Craik D. J.; Norton R. S. Protein Sci. 1994, 3, 1833. pmid: 7849598
[99]	Norton R. S.; Pallaghy P. K. Toxicon 1998, 36, 1573. doi: 10.1016/s0041-0101(98)00149-4 pmid: 9792173
[100]	Saez N. J.; Mobli M.; Bieri M.; Chassagnon I. R.; Malde A. K.; Gamsjaeger R.; Mark A. E.; Gooley P. R.; Rash L. D.; King G. F. Mol. Pharmacol. 2011, 80, 796.
[101]	Baron A.; Diochot S.; Salinas M.; Deval E.; Noël J.; Lingueglia E. Toxicon 2013, 75, 187. doi: 10.1016/j.toxicon.2013.04.008 pmid: 23624383
[102]	Kini R. M.; Doley R. Toxicon 2010, 56, 855.
[103]	Mourier G.; Salinas M.; Kessler P.; Stura E. A.; Leblanc M.; Tepshi L.; Besson T.; Diochot S.; Baron A.; Douguet D.; Lingueglia E.; Servent D. J. Biol. Chem. 2016, 291, 2616. doi: 10.1074/jbc.M115.702373 pmid: 26680001
[104]	Chagot B.; Escoubas P.; Diochot S.; Bernard C.; Lazdunski M.; Darbon H. Protein Sci. 2005, 14, 2003.
[105]	Jensen J. E.; Cristofori-Armstrong B.; Anangi R.; Rosengren K. J.; Lau C. H. Y.; Mobli M.; Brust A.; Alewood P. F.; King G. F.; Rash L. D. J. Med. Chem. 2014, 57, 9195. doi: 10.1021/jm501400p pmid: 25337890
[106]	Cristofori-Armstrong B.; Saez N. J.; Chassagnon I. R.; King G. F.; Rash L. D. Biochem. Pharmacol. 2019, 163, 381. doi: S0006-2952(19)30090-5 pmid: 30849303
[107]	Chen X.; Kalbacher H.; Gründer S. J. Gen. Physiol. 2005, 126, 71.
[108]	Sherwood T. W.; Lee K. G.; Gormley M. G.; Askwith C. C. J. Neurosci. 2011, 31, 9723. doi: 10.1523/JNEUROSCI.1665-11.2011 pmid: 21715637
[109]	Chen X.; Kalbacher H.; Gründer S. J. Gen. Physiol. 2006, 127, 267.
[110]	Hoagland E. N.; Sherwood T. W.; Lee K. G.; Walker C. J.; Askwith C. C. J. Biol. Chem. 2010, 285, 41852. doi: 10.1074/jbc.M110.171330 pmid: 21036899
[111]	Dawson R. J. P.; Benz J.; Stohler P.; Tetaz T.; Joseph C.; Huber S.; Schmid G.; Hügin D.; Pflimlin P.; Trube G.; Rudolph M. G.; Hennig M.; Ruf A. Nat. Commun. 2012, 3, 936. doi: 10.1038/ncomms1917 pmid: 22760635
[112]	Liu Y.; Hagan R.; Schoellerman J. Sci. Rep. 2018, 8, 7179. doi: 10.1038/s41598-018-25386-9 pmid: 29739981

靶向酸敏感离子通道的毒素肽: 镇痛机制与生物合成开发

Targeting Acid-Sensing Ion Channels with Toxin Peptides: Analgesic Mechanisms and Biosynthesis Development

RichHTML

PDF

可视化

摘要/Abstract

引用此文

分享此文

图/表 9

参考文献 112

相关文章 6

编辑推荐

相关统计

本文评价

[1]	夏志强,黄敬坚,汪猷. 青蒿素生物合成的研究II. 前体[15-^2H]-和[15-^3H]-青蒿酸的化学合成[J]. 化学学报, 1991, 49(12): 1514-1518.
[2]	易国良,蒋丽金,马金石. 藻胆蛋白生物合成的模型反应I. 藻蓝胆素硫醚键的形成[J]. 化学学报, 1991, 49(1): 94-97.
[3]	黄敬坚,周风仪,吴莲芬,曾桂辉. 青蒿素生物合成的研究1. 青蒿素体内青蒿酸的生物合成[J]. 化学学报, 1990, 48(3): 275-277.
[4]	戚生初,孙平侠,李,王文清,赵永和,张茂良,吴季兰. HCN-H2O气体混合物放电化学: 研究放电能作用下生物分子生成[J]. 化学学报, 1989, 47(1): 57-59.
[5]	汪猷,夏志强,周凤仪,吴毓林,黄敬坚,王执中. 青蒿素生物合成的研究III: 青蒿素和青蒿素B生物合成中的关键性中间体-青蒿素[J]. 化学学报, 1988, 46(11): 1152-1153.
[6]	黄敬坚,NICHOLLS,K.M,陈朝环,汪猷. 青蒿素的二维核磁共振研究[J]. 化学学报, 1987, 45(3): 305-308.