Treating autoimmune disorders with venom-derived peptides

References

• Wahren-Herlenius M, Dörner T. Immunopathogenic mechanisms of systemic autoimmune disease. Lancet. 2013;382(9894):819–831. DOI:10.1016/S0140-6736(13)60954-X
   PubMed Web of Science ®Google Scholar
• Hayter SM, Cook MC. Updated assessment of the prevalence, spectrum and case definition of autoimmune disease. Autoimmun Rev. 2012;11(10):754–765. DOI:10.1016/j.autrev.2012.02.001
   PubMed Web of Science ®Google Scholar
• Chatenoud L. Precision medicine for autoimmune disease. Nat Biotechnol. 2016;34(9):930–932. DOI:10.1038/nbt.3670
   PubMed Web of Science ®Google Scholar
• Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med. 2002;347(12):911–920. DOI:10.1056/NEJMra020100
   PubMed Web of Science ®Google Scholar
• Rose NR. Prediction and prevention of autoimmune disease in the 21st century: a review and preview. Am J Epidemiol. 2016;183(5):403–406. DOI:10.1093/aje/kwv292
   PubMed Web of Science ®Google Scholar
• Chatenoud L. Biotherapies targeting T and B cells: from immune suppression to immune tolerance. Curr Opin Pharmacol. 2015;23:92–97. DOI:10.1016/j.coph.2015.05.013
   PubMed Web of Science ®Google Scholar
• Ghanshani S, Wulff H, Miller MJ, et al. Up-regulation of the IKCa1 potassium channel during T-cell activation molecular mechanism and functional consequences. J Biol Chem. 2000;275(47):37137–37149. DOI:10.1074/jbc.M003941200
   PubMed Web of Science ®Google Scholar
• Cahalan MD, Wulff H, Chandy KG. Molecular properties and physiological roles of ion channels in the immune system. J Clin Immunol. 2001;21(4):235–252.
   PubMed Web of Science ®Google Scholar
• Jang SH, Byun JK, Jeon WI, et al. Nuclear localization and functional characteristics of voltage-gated potassium channel Kv1.3. J Biol Chem. 2015;290(20):12547–12557. DOI:10.1074/jbc.M114.561324
   PubMed Web of Science ®Google Scholar
• Kazama I. Physiological significance of delayed rectifier K(+) channels (Kv1.3) expressed in T lymphocytes and their pathological significance in chronic kidney disease. J Physiol Sci. 2015;65(1):25–35. DOI:10.1007/s12576-014-0331-x
   PubMed Web of Science ®Google Scholar
• Panyi G, Varga Z, Gáspár R. Ion channels and lymphocyte activation. Immunol Lett. 2004;92(1–2):55–66. DOI:10.1016/j.imlet.2003.11.020
   PubMed Web of Science ®Google Scholar
• Chandy KG, Wulff H, Beeton C, et al. K+ channels as targets for specific immunomodulation. Trends Pharmacol Sci. 2004;25(5):280–289. DOI:10.1016/j.tips.2004.03.010
   PubMed Web of Science ®Google Scholar
• Wang J, Xiang M. Targeting potassium channels Kv1.3 and KCa 3.1: routes to selective immunomodulators in autoimmune disorder treatment? Pharmacotherapy. 2013;33(5):515–528. DOI:10.1002/phar.1236
   PubMed Web of Science ®Google Scholar
• Pérez-Verdaguer M, Capera J, Serrano-Novillo C, et al. The voltage-gated potassium channel Kv1.3 is a promising multitherapeutic target against human pathologies. Expert Opin Ther Targets. 2016;20(5):577–591. DOI:10.1517/14728222.2016.1112792
   PubMed Web of Science ®Google Scholar
• Damjanovich S, Gáspár R, Panyi G. An alternative to conventional immunosuppression: small-molecule inhibitors of Kv1.3 channels. Mol Interv. 2004;4(5):250–254. DOI:10.1124/mi.4.5.4
   PubMedGoogle Scholar
• Hanson DC, Nguyen A, Mather RJ, et al. UK-78,282, a novel piperidine compound that potently blocks the Kv1.3 voltage-gated potassium channel and inhibits human T cell activation. Br J Pharmacol. 1999;126(8):1707–1716. DOI:10.1038/sj.bjp.0702480
   PubMed Web of Science ®Google Scholar
• Schmitz A, Sankaranarayanan A, Azam P, et al. Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases. Mol Pharmacol. 2005;68(5):1254–1270. DOI:10.1124/mol.105.015669
   PubMed Web of Science ®Google Scholar
• Koo GC, Blake JT, Shah K, et al. Correolide and derivatives are novel immunosuppressants blocking the lymphocyte Kv1.3 potassium channels. Cell Immunol. 1999;197(2):99–107. DOI:10.1006/cimm.1999.1569
   PubMed Web of Science ®Google Scholar
• Nguyen A, Kath JC, Hanson DC, et al. Novel nonpeptide agents potently block the C-type inactivated conformation of Kv1.3 and suppress T cell activation. Mol Pharmacol. 1996;50(6):1672–1679.
   PubMed Web of Science ®Google Scholar
• Watanabe K, Iwasaki K, Abe T, et al. Enantioselective total synthesis of (-)-candelalide A, a novel blocker of the voltage-gated potassium channel Kv1.3 for an immunosuppressive agent. Org Lett. 2005;7(17):3745–3748. DOI:10.1021/ol051398c
   PubMed Web of Science ®Google Scholar
• Pennington M. ShK-186 from discovery to clinical development. Toxicon. 2013;75(8):211. DOI:10.1016/j.toxicon.2013.08.020
   Web of Science ®Google Scholar
• Chandy KG, DeCoursey TE, Cahalan MD, et al. Voltage-gated potassium channels are required for human T lymphocyte activation. J Exp Med. 1984;160(2):369–385.
   PubMed Web of Science ®Google Scholar
• DeCoursey TE, Chandy KG, Gupta S, et al. Voltage-gated K+ channels in human T lymphocytes: a role in mitogenesis? Nature. 1984;307(5950):465–468.
   PubMed Web of Science ®Google Scholar
• Sallusto F, Geginat J, Lanzavecchia A, et al. Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol. 2004;22:745–763. DOI:10.1146/annurev.immunol.22.012703.104702
   PubMed Web of Science ®Google Scholar
• Wulff H, Knaus HG, Pennington M, et al. K+ channel expression during B cell differentiation: implications for immunomodulation and autoimmunity. J Immunol. 2004;173(2):776–786. DOI:10.4049/jimmunol.173.2.776
   PubMed Web of Science ®Google Scholar
• Wulff H, Calabresi PA, Allie R, et al. The voltage-gated Kv1.3 K(+) channel in effector memory T cells as new target for MS. J Clin Invest. 2003;111(11):1703–1713. DOI:10.1172/JCI16921
   PubMed Web of Science ®Google Scholar
• Beeton C, Wulff H, Standifer NE, et al. Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. Proc Natl Acad Sci U S A. 2006;103(46):17414–17419. DOI:10.1073/pnas.0605136103
   PubMed Web of Science ®Google Scholar
• Toldi G, Bajnok A, Dobi D, et al. The effects of Kv1.3 and IKCa1 potassium channel inhibition on calcium influx of human peripheral T lymphocytes in rheumatoid arthritis. Immunobiology. 2013;218(3):311–316. DOI:10.1016/j.imbio.2012.05.013
   PubMed Web of Science ®Google Scholar
• Toldi G, Vásárhelyi B, Kaposi A, et al. Lymphocyte activation in type 1 diabetes mellitus: the increased significance of Kv1.3 potassium channels. Immunol Lett. 2010;133(1):35–41. DOI:10.1016/j.imlet.2010.06.009
   PubMed Web of Science ®Google Scholar
• Nicolaou SA, Szigligeti P, Neumeier L, et al. Altered dynamics of Kv1.3 channel compartmentalization in the immunological synapse in systemic lupus erythematosus. J Immunol. 2007;179(1):346–356. DOI:10.4049/jimmunol.179.1.346
   PubMed Web of Science ®Google Scholar
• Carbone E, Wanke E, Prestipino G, et al. Selective blockage of voltage-dependent K+ channels by a novel scorpion toxin. Nature. 1982;296(5852):90–91. DOI:10.1038/296090a0
   PubMed Web of Science ®Google Scholar
• Sitges M, Possani LD, Bayón A. Noxiustoxin, a short-chain toxin from the Mexican scorpion Centruroides noxius, induces transmitter release by blocking K+ permeability. J Neurosci. 1986;6(6):1570–1574.
   PubMed Web of Science ®Google Scholar
• Shieh CC, Coghlan M, Sullivan JP, et al. Potassium channels: molecular defects, diseases, and therapeutic opportunities. Pharmacol Rev. 2000;52(4):557–594.
   PubMed Web of Science ®Google Scholar
• Kalman K, Pennington MW, Lanigan MD, et al. ShK-Dap22, a potent Kv1.3-specific immunosuppressive polypeptide. J Biol Chem. 1998;273(49):32697–32707. DOI:10.1074/jbc.273.49.32697
   PubMed Web of Science ®Google Scholar
• Lanigan MD, Michael W, Lefievre PY, et al. Designed peptide analogues of the potassium channel blocker ShK toxin. Biochemistry. 2001;40(51):15528–15537. DOI:10.1021/bi011300b
   PubMed Web of Science ®Google Scholar
• Possani LD, Martin BM, Svendsen IB. The primary structure of noxiustoxin: a K+, channel blocking peptide, purified from the venom of the scorpion Centruroides noxius Hoffmann. Carlsberg Res Commun. 1982;47(5):285–289. DOI:10.1007/BF02907789
   Google Scholar
• Harvey AJ, Gable RW, Baell JB. A three-residue, continuous binding epitope peptidomimetic of ShK toxin as a Kv1.3 inhibitor. Bioorg Med Chem Lett. 2005;15(13):3193–3196. DOI:10.1016/j.bmcl.2005.05.014
   PubMed Web of Science ®Google Scholar
• Baell JB, Harvey AJ, Norton RS. Design and synthesis of type-III mimetics of ShK toxin. J Comput Aided Mol Des. 2002;16(4):245–262.
   PubMed Web of Science ®Google Scholar
• Beeton C, Pennington MW, Wulff H, et al. Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases. Mol Pharmacol. 2005;67(4):1369–1381. DOI:10.1124/mol.104.00819341
   PubMed Web of Science ®Google Scholar
• Pennington MW, Beeton C, Galea CA, et al. Engineering a stable and selective peptide blocker of the Kv1.3 channel in T lymphocytes. Mol Pharmacol. 2009;75(4):762–773. DOI:10.1124/mol.108.052704
   PubMed Web of Science ®Google Scholar
• Beeton C, Smith BJ, Sabo JK, et al. The D-diastereomer of ShK toxin selectively blocks voltage-gated K+ channels and inhibits T lymphocyte proliferation. J Biol Chem. 2008;283(2):988–997. DOI:10.1074/jbc.M706008200
   PubMed Web of Science ®Google Scholar
• Cao Z, Yu Y, Wu Y, et al. The genome of Mesobuthus martensii reveals a unique adaptation model of arthropods. Nat Commun. 2013;4(10):2602. DOI:10.1038/ncomms3602
   PubMed Web of Science ®Google Scholar
• Castañeda O, Sotolongo V, Amor AM, et al. Characterization of a potassium channel toxin from the Caribbean Sea anemone Stichodactyla helianthus. Toxicon. 1995;33(5):603–613. DOI:10.1016/0041-0101(95)00013-C
   PubMed Web of Science ®Google Scholar
• Renisio JG, Romi-Lebrun R, Blanc E, et al. Solution structure of BmKTX, a K+ blocker toxin from the Chinese scorpion Buthus Martensi. Proteins. 2000;38(1):70–78. DOI:10.1002/(SICI)1097-0134(20000101)38:1<70::AID-PROT8>3.0.CO;2-5
   PubMed Web of Science ®Google Scholar
• Jaravine VA, Nolde DE, Reibarkh MJ, et al. Three-dimensional structure of toxin OSK1 from Orthochirus scrobiculosus scorpion venom. Biochemistry. 1997;36(6):1223–1232. DOI:10.1021/bi9614390
   PubMed Web of Science ®Google Scholar
• Mouhat S, Visan V, Ananthakrishnan S, et al. K+ channel types targeted by synthetic OSK1, a toxin from Orthochirus scrobiculosus scorpion venom. Biochem J. 2005;385(Pt 1):95–104. DOI:10.1042/BJ20041379
   PubMed Web of Science ®Google Scholar
• Savarin P, Romi-Lebrun R, Zinn-Justin S, et al. Structural and functional consequences of the presence of a fourth disulfide bridge in the scorpion short toxins: solution structure of the potassium channel inhibitor HsTX1. Protein Sci. 1999;8(12):2672–2685. DOI:10.1110/ps.8.12.2672
   PubMed Web of Science ®Google Scholar
• Crest M, Jacquet G, Gola M, et al. Kaliotoxin, a novel peptidyl inhibitor of neuronal BK-type Ca(2+)-activated K+ channels characterized from Androctonus mauretanicus mauretanicus venom. J Biol Chem. 1992;267(3):1640–1647.
   PubMed Web of Science ®Google Scholar
• Gairí M, Romi R, Fernández I, et al. 3D structure of kaliotoxin: is residue 34 a key for channel selectivity? J Pept Sci. 1997;3(4):314–319. DOI:10.1002/(SICI)1099-1387(199707)3:4<314::AID-PSC117>3.0.CO;2-E
   PubMed Web of Science ®Google Scholar
• Kharrat R, Mansuelle P, Sampieri F, et al. Maurotoxin, a four-disulfide bridge toxin from Scorpio maurus venom: purification, structure and action on potassium channels. FEBS Lett. 1997;406(3):284–290. DOI:10.1016/S0014-5793(97)00285-8
   PubMed Web of Science ®Google Scholar
• Blanc E, Sabatier JM, Kharrat R, et al. Solution structure of maurotoxin, a scorpion toxin from Scorpio maurus, with high affinity for voltage-gated potassium channels. Proteins. 1997;29(3):321–333.
   PubMed Web of Science ®Google Scholar
• Gimenez-Gallego G, Navia MA, Reuben JP, et al. Purification, sequence, and model structure of charybdotoxin, a potent selective inhibitor of calcium-activated potassium channels. Proc Natl Acad Sci U S A. 1988;85(10):3329–3333.
   PubMed Web of Science ®Google Scholar
• Dauplais M, Gilquin B, Possani LD, et al. Determination of the three-dimensional solution structure of noxiustoxin: analysis of structural differences with related short-chain scorpion toxins. Biochemistry. 1995;34(51):16563–16573.
   PubMed Web of Science ®Google Scholar
• Garcia-Calvo M, Leonard RJ, Novick J, et al. Purification, characterization, and biosynthesis of margatoxin, a component of Centruroides margaritatus venom that selectively inhibits voltage-dependent potassium channels. J Biol Chem. 1993;268(25):18866–18874.
   PubMed Web of Science ®Google Scholar
• Johnson BA, Stevens SP, Williamson JM. Determination of the three-dimensional structure of margatoxin by 1H, 13C, 15N triple-resonance nuclear magnetic resonance spectroscopy. Biochemistry. 1994;3(50):15061–15070.
   Web of Science ®Google Scholar
• Péter M Jr, Hajdu P, Varga Z, et al. Blockage of human T lymphocyte Kv1.3 channels by Pi1, a novel class of scorpion toxin. Biochem Biophys Res Commun. 2000;278(1):34–37. DOI:10.1006/bbrc.2000.3756
   PubMed Web of Science ®Google Scholar
• Gómez-Lagunas F, Olamendi-Portugal T, Zamudio FZ, et al. Two novel toxins from the venom of the scorpion Pandinus imperator show that the N-terminal amino acid sequence is important for their affinities towards Shaker B K+ channels. J Membr Biol. 1996;152(1):49–56.
   PubMed Web of Science ®Google Scholar
• Batista CV, Gómez-Lagunas F, Rodríguez De La Vega RC, et al. Two novel toxins from the Amazonian scorpion Tityus cambridgei that block Kv1.3 and Shaker B K(+)-channels with distinctly different affinities. Biochim Biophys Acta. 2002;1601(2):123–131. DOI:10.1016/S1570-9639(02)00458-2
   PubMed Web of Science ®Google Scholar
• Srinivasan KN, Sivaraja V, Huys I, et al. kappa-Hefutoxin1, a novel toxin from the scorpion Heterometrus fulvipes with unique structure and function. Importance of the functional diad in potassium channel selectivity. J Biol Chem. 2002;277(33):30040–30047. DOI:10.1074/jbc.M111258200
   PubMed Web of Science ®Google Scholar
• Rodrigues AR, Arantes EC, Monje F, et al. Tityustoxin-K(alpha) blockade of the voltage-gated potassium channel Kv1.3. Br J Pharmacol. 2003;139(6):1180–1186. DOI:10.1038/sj.bjp.0705343
   PubMed Web of Science ®Google Scholar
• Ellis KC, Tenenholz TC, Jerng H, et al. Interaction of a toxin from the scorpion Tityus serrulatus with a cloned K+ channel from squid (sqKv1A). Biochemistry. 2001;40(20):5942–5953. DOI:10.1021/bi010173g
   PubMed Web of Science ®Google Scholar
• Bagdány M, Batista CV, Valdez-Cruz NA, et al. Anuroctoxin, a new scorpion toxin of the alpha-KTx 6 subfamily, is highly selective for Kv1.3 over IKCa1 ion channels of human T lymphocytes. Mol Pharmacol. 2005;67(4):1034–1044. DOI:10.1124/mol.104.007187
   PubMed Web of Science ®Google Scholar
• Olamendi-Portugal T, Somodi S, Fernández JA, et al. Novel alpha-KTx peptides from the venom of the scorpion Centruroides elegans selectively blockade Kv1.3 over IKCa1 K+ channels of T cells. Toxicon. 2005;46(4):418–429. DOI:10.1016/j.toxicon.2005.06.001
   PubMed Web of Science ®Google Scholar
• Abdel-Mottaleb Y, Coronas FV, De Roodt AR, et al. A novel toxin from the venom of the scorpion Tityus trivittatus is the first member of a new alpha-KTX subfamily. FEBS Lett. 2006;580(2):592–659. DOI:10.1016/j.febslet.2005.12.073
   PubMed Web of Science ®Google Scholar
• Abbas N, Belghazi M, Abdel-Mottaleb Y, et al. A new Kaliotoxin selective towards Kv1.3 and Kv1.2 but not Kv1.1 channels expressed in oocytes. Biochem Biophys Res Commun. 2008;376(3):525–530. DOI:10.1016/j.bbrc.2008.09.033
   PubMed Web of Science ®Google Scholar
• Corzo G, Papp F, Varga Z, et al. A selective blocker of Kv1.2 and Kv1.3 potassium channels from the venom of the scorpion Centruroides suffusus suffusus. Biochem Pharmacol. 2008;76(9):1142–1154. DOI:10.1016/j.bcp.2008.08.018
   PubMed Web of Science ®Google Scholar
• Shijin Y, Hong Y, Yibao M, et al. Characterization of a new Kv1.3 channel-specific blocker, J123, from the scorpion Buthus martensii Karsch. Peptides. 2008;29(9):1514–1520. DOI:10.1016/j.peptides.2008.04.021
   PubMed Web of Science ®Google Scholar
• Abdel-Mottaleb Y, Vandendriessche T, Clynen E, et al. OdK2, a Kv1.3 channel-selective toxin from the venom of the Iranian scorpion Odonthobuthus doriae. Toxicon. 2008;51(8):1424–1430. DOI:10.1016/j.toxicon.2008.03.027
   PubMed Web of Science ®Google Scholar
• Papp F, Batista CV, Varga Z, et al. Tst26, a novel peptide blocker of Kv1.2 and Kv1.3 channels from the venom of Tityus stigmurus. Toxicon. 2009;54(4):379–389. DOI:10.1016/j.toxicon.2009.05.023
   PubMed Web of Science ®Google Scholar
• Chen Z, Hu Y, Han S, et al. ImKTx1, a new Kv1.3 channel blocker with a unique primary structure. J Biochem Mol Toxicol. 2011;25(4):244–251. DOI:10.1002/jbt.20382
   PubMed Web of Science ®Google Scholar
• Han S, Hu Y, Zhang R, et al. ImKTx88, a novel selective Kv1.3 channel blocker derived from the scorpion Isometrus maculates. Toxicon. 2011;57(2):348–355. DOI:10.1016/j.toxicon.2010.12.015
   PubMed Web of Science ®Google Scholar
• Chen ZY, Hu YT, Yang WS, et al. Hg1, novel peptide inhibitor specific for Kv1.3 channels from first scorpion Kunitz-type potassium channel toxin family. J Biol Chem. 2012;287(17):13813–13821. DOI:10.1074/jbc.M112.343996
   PubMed Web of Science ®Google Scholar
• Chen Z, Luo F, Feng J, et al. Genomic and structural characterization of Kunitz-type peptide LmKTT-1a highlights diversity and evolution of scorpion potassium channel toxins. PLoS One. 2013;8(4):e60201. DOI:10.1371/journal.pone.0060201
   PubMed Web of Science ®Google Scholar
• Varga Z, Gurrola-Briones G, Papp F, et al. Vm24, a natural immunosuppressive peptide, potently and selectively blocks Kv1.3 potassium channels of human T cells. Mol Pharmacol. 2012;82(3):372–382. DOI:10.1124/mol.112.078006
   PubMed Web of Science ®Google Scholar
• Gurrola GB, Hernández-López RA, Rodríguez De La Vega RC, et al. Structure, function, and chemical synthesis of Vaejovis mexicanus peptide 24: a novel potent blocker of Kv1.3 potassium channels of human T lymphocytes. Biochemistry. 2012;51(19):4049–4061. DOI:10.1021/bi300060n
   PubMed Web of Science ®Google Scholar
• Meng L, Xie Z, Zhang Q, et al. Scorpion potassium channel-blocking defensin highlights a functional link with neurotoxin. J Biol Chem. 2016;291(13):7097–7106. DOI:10.1074/jbc.M115.680611
   PubMed Web of Science ®Google Scholar
• Tudor JE, Pallaghy PK, Pennington MW, et al. Solution structure of ShK toxin, a novel potassium channel inhibitor from a sea anemone. Nat Struct Biol. 1996;3(4):317–320. DOI:10.1038/nsb0496-317
   PubMedGoogle Scholar
• Aneiros A, García I, Martínez JR, et al. A potassium channel toxin from the secretion of the sea anemone Bunodosoma granulifera. Isolation, amino acid sequence and biological activity. Biochim Biophys Acta. 1993;1157(1):86–92.
   PubMed Web of Science ®Google Scholar
• Dauplais M, Lecoq A, Song J, et al. On the convergent evolution of animal toxins. Conservation of a diad of functional residues in potassium channel-blocking toxins with unrelated structures. J Biol Chem. 1997;272(7):4302–4309. DOI:10.1074/jbc.272.7.4302
   PubMed Web of Science ®Google Scholar
• Yang W, Feng J, Wang B, et al. BF9, the first functionally characterized snake toxin peptide with Kunitz-type protease and potassium channel inhibiting properties. J Biochem Mol Toxicol. 2014;28(2):76–83. DOI:10.1002/jbt.21538
   PubMed Web of Science ®Google Scholar
• Giangiacomo KM, Ceralde Y, Mullmann TJ. Molecular basis of alpha-KTx specificity. Toxicon. 2004;43(8):877–886. DOI:10.1016/j.toxicon.2003.11.029
   PubMed Web of Science ®Google Scholar
• Chi V, Pennington MW, Norton RS, et al. Development of a sea anemone toxin as an immunomodulator for therapy of autoimmune diseases. Toxicon. 2012;59(4):529–546. DOI:10.1016/j.toxicon.2011.07.016
   PubMed Web of Science ®Google Scholar
• Mouhat S, Teodorescu G, Homerick D, et al. Pharmacological profiling of Orthochirus scrobiculosus toxin 1 analogs with a trimmed N-terminal domain. Mol Pharmacol. 2006;69(1):354–362. DOI:10.1124/mol.105.017210
   PubMed Web of Science ®Google Scholar
• Romi-Lebrun R, Lebrun B, Martin-Eauclaire MF, et al. Purification, characterization, and synthesis of three novel toxins from the Chinese scorpion Buthus martensi, which act on K+ channels. Biochemistry. 1997;36(44):13473–13482. DOI:10.1021/bi971044w
   PubMed Web of Science ®Google Scholar
• Han S, Yin S, Yi H, et al. Protein-protein recognition control by modulating electrostatic interactions. J Proteome Res. 2010;9(6):3118–3125. DOI:10.1021/pr100027k
   PubMed Web of Science ®Google Scholar
• Chen Z, Hu Y, Hu J, et al. Unusual binding mode of scorpion toxin BmKTX onto potassium channels relies on its distribution of acidic residues. Biochem Biophys Res Commun. 2014;447(1):70–76. DOI:10.1016/j.bbrc.2014.03.101
   PubMed Web of Science ®Google Scholar
• Ye F, Hu Y, Yu W, et al. The scorpion toxin analogue BmKTX-D33H as a potential Kv1.3 channel-selective immunomodulator for autoimmune diseases. Toxins (Basel). 2016;8(4):115. DOI:10.3390/toxins8040115
   PubMed Web of Science ®Google Scholar
• Han S, Yi H, Yin SJ, et al. Structural basis of a potent peptide inhibitor designed for Kv1.3 channel, a therapeutic target of autoimmune disease. J Biol Chem. 2008;283(27):19058–19065. DOI:10.1074/jbc.M802054200
   PubMed Web of Science ®Google Scholar
• Chen Z, Hu Y, Hong J, et al. Toxin acidic residue evolutionary function-guided design of de novo peptide drugs for the immunotherapeutic target, the Kv1.3 channel. Sci Rep. 2015;5:9881. DOI:10.1038/srep09881
   PubMed Web of Science ®Google Scholar
• Yin SJ, Jiang L, Yi H, et al. Different residues in channel turret determining the selectivity of ADWX-1 inhibitor peptide between Kv1.1 and Kv1.3 channels. J Proteome Res. 2008;7(11):4890–4897. DOI:10.1021/pr800494a
   PubMed Web of Science ®Google Scholar
• Bartok A, Fehér K, Bodor A, et al. An engineered scorpion toxin analogue with improved Kv1.3 selectivity displays reduced conformational flexibility. Sci Rep. 2015;5:18397. DOI:10.1038/srep18397
   PubMed Web of Science ®Google Scholar
• Vingsbo C, Sahlstrand P, Brun JG, et al. Pristane-induced arthritis in rats: a new model for rheumatoid arthritis with a chronic disease course influenced by both major histocompatibility complex and non-major histocompatibility complex genes. Am J Pathol. 1996;149(5):1675–1683.
   PubMed Web of Science ®Google Scholar
• Racke MK. Experimental autoimmune encephalomyelitis (EAE). Curr Protoc Neurosci. 2001. 9:9.7. doi: 10.1002/0471142301.ns0907s14 Chapter 9:Unit9.7. 2001.
   PubMedGoogle Scholar
• Tarcha EJ, Chi V, Muñoz-Elías EJ, et al. Durable pharmacological responses from the peptide ShK-186, a specific Kv1.3 channel inhibitor that suppresses T cell mediators of autoimmune disease. J Pharmacol Exp Ther. 2012;342(3):642–653. DOI:10.1124/jpet.112.191890
   PubMed Web of Science ®Google Scholar
• Norton RS, Pennington MW, Beeton C. Transforming a toxin into a therapeutic: the sea anemone potassium channel blocker ShK toxin for treatment of autoimmune diseases. In: King GF, editor Venoms to drugs: venom as a source for the development of human therapeutics. London: Royal Society of Chemistry; 2015.
   Google Scholar
• Li Z, Liu WH, Han S, et al. Selective inhibition of CCR7(-) effector memory T cell activation by a novel peptide targeting Kv1.3 channel in a rat experimental autoimmune encephalomyelitis model. J Biol Chem. 2012;287(35):29479–29494. DOI:10.1074/jbc.M112.379594
   PubMed Web of Science ®Google Scholar
• Hou P, Zhang R, Liu Y, et al. Physiological role of Kv1.3 channel in T lymphocyte cell investigated quantitatively by kinetic modeling. PLoS One. 2014;9(3):e89975. DOI:10.1371/journal.pone.0089975
   PubMed Web of Science ®Google Scholar
• Feng J, Yang W, Xie Z, et al. Kv channel S1-S2 linker working as a binding site of human β-defensin 2 for channel activation modulation. J Biol Chem. 2015;290(25):15487–15495. DOI:10.1074/jbc.M115.639500
   PubMed Web of Science ®Google Scholar
• Xie Z, Feng J, Yang W, et al. Human α-defensins are immune-related Kv1.3 channel inhibitors: new support for their roles in adaptive immunity. FASEB J. 2015;29(10):4324–4333. DOI:10.1096/fj.15-274787
   PubMed Web of Science ®Google Scholar