OpenLB
Open Library of Bioscience
Advanced Search
Toxins
01 18, 2024;16 (1):

Voltage-Gated Sodium Channel Inhibition by µ-Conotoxins.

Kirsten L McMahon, Irina Vetter, Christina I Schroeder
Author Information
  1. Kirsten L McMahon: Institute for Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia.
  2. Irina Vetter: Institute for Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia. ORCID
  3. Christina I Schroeder: Institute for Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia. ORCID
PMID: 38251271 DOI: 10.3390/toxins16010055

Abstract

µ-Conotoxins are small, potent pore-blocker inhibitors of voltage-gated sodium (Na) channels, which have been identified as pharmacological probes and putative leads for analgesic development. A limiting factor in their therapeutic development has been their promiscuity for different Na channel subtypes, which can lead to undesirable side-effects. This review will focus on four areas of µ-conotoxin research: (1) mapping the interactions of µ-conotoxins with different Na channel subtypes, (2) µ-conotoxin structure-activity relationship studies, (3) observed species selectivity of µ-conotoxins and (4) the effects of µ-conotoxin disulfide connectivity on activity. Our aim is to provide a clear overview of the current status of µ-conotoxin research.

Keywords

disulfide-rich peptide peptide structure–activity relationships subtype selectivity venom peptide voltage-gated sodium channels µ-conotoxin

References

  1. Mar Drugs. 2019 Aug 29;17(9): [PMID: 31470595]
  2. Eur J Med Chem. 2013 Jul;65:144-50 [PMID: 23707919]
  3. Front Pharmacol. 2018 Aug 07;9:880 [PMID: 30131702]
  4. J Biol Chem. 1991 Sep 15;266(26):16989-91 [PMID: 1654319]
  5. FEBS J. 2014 Jul;281(13):2885-98 [PMID: 24814369]
  6. J Biol Chem. 2012 Sep 7;287(37):31382-92 [PMID: 22773842]
  7. J Am Chem Soc. 2008 Oct 29;130(43):14280-6 [PMID: 18831583]
  8. Br J Pharmacol. 2012 Jul;166(5):1654-68 [PMID: 22229737]
  9. Mar Drugs. 2022 Apr 23;20(5): [PMID: 35621933]
  10. ACS Omega. 2018 Oct 31;3(10):12330-12340 [PMID: 30411002]
  11. Science. 2017 Mar 3;355(6328): [PMID: 28183995]
  12. PLoS One. 2014 Mar 27;9(3):e93267 [PMID: 24676211]
  13. Bioorg Med Chem Lett. 2013 Sep 1;23(17):4892-5 [PMID: 23891024]
  14. J Biol Chem. 2003 Mar 7;278(10):8717-24 [PMID: 12471026]
  15. Toxicon. 2009 Jan;53(1):90-8 [PMID: 18950653]
  16. Biochemistry. 1998 Mar 31;37(13):4407-19 [PMID: 9521760]
  17. Mar Drugs. 2019 Jul 02;17(7): [PMID: 31269696]
  18. Mol Pharmacol. 2011 Oct;80(4):573-84 [PMID: 21709136]
  19. Br J Pharmacol. 2013 Apr;168(7):1597-610 [PMID: 23146020]
  20. Biochem Biophys Res Commun. 2001 May 4;283(2):374-8 [PMID: 11327711]
  21. Anal Chem. 2012 Jan 3;84(1):262-6 [PMID: 22126836]
  22. Mol Pharmacol. 2002 May;61(5):1192-201 [PMID: 11961138]
  23. Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10302-7 [PMID: 21652775]
  24. Biophys J. 1998 Jul;75(1):236-46 [PMID: 9649383]
  25. Biophys J. 2012 Feb 8;102(3):483-8 [PMID: 22325270]
  26. Br J Pharmacol. 2009 Nov;158(6):1413-25 [PMID: 19845672]
  27. Channels (Austin). 2009 Jan-Feb;3(1):32-8 [PMID: 19221510]
  28. J Med Chem. 2015 Sep 24;58(18):7093-118 [PMID: 25927480]
  29. Biochemistry. 2008 Oct 14;47(41):10940-9 [PMID: 18798648]
  30. FEBS Lett. 2005 Jul 18;579(18):3881-4 [PMID: 15990094]
  31. Toxicon. 2006 Jan;47(1):122-32 [PMID: 16325217]
  32. Neuropharmacology. 2011 Jul-Aug;61(1-2):105-11 [PMID: 21419143]
  33. Anal Chem. 2018 Mar 6;90(5):3321-3327 [PMID: 29397705]
  34. Biomedicines. 2020 Oct 02;8(10): [PMID: 33023152]
  35. Toxicon. 2020 Oct 30;186:29-34 [PMID: 32758497]
  36. J Mol Graph. 1996 Feb;14(1):51-5, 29-32 [PMID: 8744573]
  37. J Gen Physiol. 2002 Jan;119(1):45-54 [PMID: 11773237]
  38. J Biol Chem. 2003 Nov 21;278(47):46805-13 [PMID: 12970353]
  39. J Neurosci. 2008 Nov 12;28(46):11768-77 [PMID: 19005038]
  40. RSC Adv. 2019 Jan 3;9(2):668-674 [PMID: 35517619]
  41. Biochemistry. 2012 Dec 11;51(49):9826-35 [PMID: 23167564]
  42. Physiol Rev. 2004 Jan;84(1):41-68 [PMID: 14715910]
  43. Biopolymers. 2012;98(2):161-5 [PMID: 22733528]
  44. FEBS Lett. 2001 Aug 10;503(1):107-10 [PMID: 11513864]
  45. Biochem Pharmacol. 2008 Jun 15;75(12):2334-44 [PMID: 18486102]
  46. Mar Drugs. 2017 Sep 22;15(10): [PMID: 28937587]
  47. Biochemistry. 2010 Jun 15;49(23):4804-12 [PMID: 20459109]
  48. Mar Drugs. 2016 Nov 18;14(11): [PMID: 27869701]
  49. Toxicon. 2017 May;130:11-18 [PMID: 28219625]
  50. Nat Rev Neurol. 2020 Dec;16(12):689-705 [PMID: 33110213]
  51. Cell Mol Life Sci. 2010 Jan;67(1):17-27 [PMID: 19705062]
  52. Biochemistry. 2016 Mar 29;55(12):1929-38 [PMID: 26959170]
  53. Biochemistry. 2002 Dec 24;41(51):15388-93 [PMID: 12484778]
  54. J Biol Chem. 2008 Aug 1;283(31):21621-8 [PMID: 18522941]
  55. J Mol Evol. 2012 Jun;74(5-6):297-309 [PMID: 22760645]
  56. Biochemistry. 2005 Jun 7;44(22):8176-86 [PMID: 15924437]
  57. J Biol Chem. 1985 Aug 5;260(16):9280-8 [PMID: 2410412]
  58. Cell Mol Life Sci. 2023 Sep 9;80(10):287 [PMID: 37689602]
  59. Biophys J. 1995 Nov;69(5):1657-65 [PMID: 8580309]
  60. Chem Biol. 2007 Apr;14(4):399-407 [PMID: 17462575]
  61. J Proteomics. 2019 Jan 6;190:12-20 [PMID: 29777871]
  62. J Physiol. 2012 Jun 1;590(11):2577-89 [PMID: 22473783]
  63. Physiol Rev. 2019 Apr 1;99(2):1079-1151 [PMID: 30672368]
  64. Biochemistry. 2005 May 17;44(19):7259-65 [PMID: 15882064]
  65. Pflugers Arch. 1994 May;427(1-2):136-42 [PMID: 8058462]
  66. Biochemistry. 1992 Sep 8;31(35):8229-38 [PMID: 1326324]
  67. Molecules. 2018 Oct 22;23(10): [PMID: 30360356]
  68. Brain Behav Evol. 2015 Sep;86(1):58-74 [PMID: 26397110]
  69. Toxins (Basel). 2014 Dec 18;6(12):3454-70 [PMID: 25529306]
  70. Expert Opin Investig Drugs. 2020 Mar;29(3):259-271 [PMID: 32070160]
  71. FEBS Lett. 1990 May 7;264(1):29-32 [PMID: 2338142]
  72. PLoS One. 2014 Aug 18;9(8):e105300 [PMID: 25133704]
  73. J Neurosci. 1998 Jun 15;18(12):4473-81 [PMID: 9614224]
  74. Mar Drugs. 2023 Mar 27;21(4): [PMID: 37103349]
  75. Chem Rev. 2019 Nov 13;119(21):11510-11549 [PMID: 31633928]
  76. ChemMedChem. 2009 Mar;4(3):406-14 [PMID: 19107760]
  77. Chem Biol Drug Des. 2015 Apr;85(4):488-93 [PMID: 25228447]
  78. J Biol Chem. 2022 Mar;298(3):101728 [PMID: 35167877]
  79. Front Pharmacol. 2023 Mar 16;14:1156855 [PMID: 37007002]
  80. Biochem Biophys Res Commun. 2017 Jan 22;482(4):1135-1140 [PMID: 27916464]
  81. J Biol Chem. 2023 Apr;299(4):103068 [PMID: 36842500]
  82. Compr Physiol. 2015 Apr;5(2):761-90 [PMID: 25880512]
  83. FEBS Lett. 1992 Sep 14;309(3):253-7 [PMID: 1325372]
  84. Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8428-33 [PMID: 24850863]
  85. FEBS J. 2011 Sep;278(18):3408-18 [PMID: 21781281]
  86. Biochemistry. 2006 Mar 21;45(11):3723-32 [PMID: 16533055]
  87. Biopolymers. 2014 Apr;101(4):347-54 [PMID: 23913763]
  88. Biochemistry. 2009 Feb 17;48(6):1210-9 [PMID: 19170536]
  89. Science. 2019 Mar 22;363(6433):1309-1313 [PMID: 30765605]
  90. Annu Rev Neurosci. 2019 Jul 8;42:87-106 [PMID: 30702961]
  91. J Biol Chem. 2007 Oct 19;282(42):30699-706 [PMID: 17724025]
  92. Science. 1985 Dec 20;230(4732):1338-43 [PMID: 4071055]
  93. Mol Pharmacol. 2007 Mar;71(3):676-85 [PMID: 17142296]
  94. Toxins (Basel). 2022 Aug 30;14(9): [PMID: 36136538]
  95. ACS Chem Biol. 2013;8(6):1344-51 [PMID: 23557677]
  96. Mar Drugs. 2018 May 07;16(5): [PMID: 29735899]
  97. J Molluscan Stud. 2015 Feb;81(1):1-23 [PMID: 26300576]
  98. Angew Chem Int Ed Engl. 2012 Apr 23;51(17):4058-61 [PMID: 22407516]
  99. Toxins (Basel). 2012 Nov 08;4(11):1236-60 [PMID: 23202314]
  100. Neuron. 1996 Feb;16(2):407-13 [PMID: 8789955]

Grants

  1. 2002860/National Health and Medical Research Council

MeSH Term

Conotoxins
Disulfides
Structure-Activity Relationship
Voltage-Gated Sodium Channels

Chemicals

Conotoxins
Disulfides
Voltage-Gated Sodium Channels
Journal Article Review

Word Cloud

Created with Highcharts 10.0.0µ-conotoxinNapeptideµ-Conotoxinsvoltage-gatedsodiumchannelsdevelopmentdifferentchannelsubtypesµ-conotoxinsselectivitysmallpotentpore-blockerinhibitorsidentifiedpharmacologicalprobesputativeleadsanalgesiclimitingfactortherapeuticpromiscuitycanleadundesirableside-effectsreviewwillfocusfourareasresearch:1mappinginteractions2structure-activityrelationshipstudies3observedspecies4effectsdisulfideconnectivityactivityaimprovideclearoverviewcurrentstatusresearchVoltage-GatedSodiumChannelInhibitiondisulfide-richstructure–activityrelationshipssubtypevenom

Similar Articles

Cited By