ライフサイエンスコーパス: conotoxin

1 diverse set of cysteine-rich peptide toxins (conotoxins).

2 the N-type calcium channel antagonist, omega-conotoxin.

3 n of the Ca(v)2.2 channel by analgesic alpha-conotoxins.

4 to thousands of bioactive peptides known as conotoxins.

5 isulfide connectivities characteristic of mu-conotoxins.

6 stinct gene families: mu-, omega-, and alpha-conotoxins.

7 tro oxidative folding and the bioactivity of conotoxins.

8 14a and the second loop of a number of alpha-conotoxins.

9 ty) in a novel framework distinct from other conotoxins.

10 d invertebrate ion channel blockers known as conotoxins.

11 t previously established for the mu- and psi-conotoxins.

12 ts have been members of the A superfamily of conotoxins.

13 rst loop affects the overall structure of mu-conotoxins.

14 etics of disulfide-bond formation of several conotoxins.

15 erlying the Nav subtype selectivity of delta-conotoxins.

16 amino acids) than the mu-, kappaM-, and psi-conotoxins (22-24 amino acids).

17 nt calcium responses were decreased by omega-conotoxin, a Cav2.2-specific inhibitor.

18 delta-Conotoxins act by inhibiting inactivation of voltage-gat

19 The new conotoxins all blocked, albeit with varying potencies, T

20 cotine addiction therapy, and the 19-residue conotoxin alpha-GID that antagonizes it.

21 alpha-Conotoxin (alpha-Ctx) MII labeling coupled with immunocy

22 We created analogs of alpha-conotoxin (alpha-Ctx) PeIA to identify ligand-receptor i

23 We previously showed that alpha-conotoxin (alpha-CTx) RgIA, one of the few alpha9alpha10

24 Current alpha-conotoxins (alpha-Ctxs) that discriminate among these nA

25 tion and reduction of disulfide bonds in two conotoxins, alpha-GI and alpha-ImI.

26 toxin subfamily, designated the short alphaA-conotoxins (alphaA(S)) and demonstrate that all of these

27 Although this conotoxin, alphaA-conotoxin OIVB (alphaA-OIVB), is a hig

28 A second series of individual alpha-conotoxin analogs based on the combinations of defined a

29 Of the 96 individual alpha-conotoxin analogs synthesized, three displayed > or =10-

30 ncert to accelerate the oxidative folding of conotoxins and modulate their conformation and function

31 is a member of the alpha-4,3 family of alpha-conotoxins and selectively blocks the alpha9alpha10 nACh

32 e-function relationships of native alphaA(S)-conotoxins and some analogues revealed a single amino ac

33 Alpha-conotoxins are a group of small, structurally defined pe

34 Many new alpha-conotoxins are being identified every year, broadening t

35 alpha-Conotoxins are disulfide-rich peptide neurotoxins that s

36 from worm hunting to fish hunting, as delta-conotoxins are highly conserved among fish hunters and c

37 alpha-Conotoxins are nAChR-targeted peptides used by Conus spe

38 on channels implicated in neurotransmission, conotoxins are of interest both as tools for pharmacolog

39 Conotoxins are of interest to neuroscientists as well as

40 alpha-Conotoxins are peptide neurotoxins isolated from venomou

41 alpha-Conotoxins are peptide toxins found in the venom of mari

42 mu-Conotoxins are peptides that block sodium channels.

43 Alpha-conotoxins are small disulfide-constrained peptides from

44 alpha-Conotoxins are subtype-selective nicotinic acetylcholine

45 lective alpha3beta4 nAChR antagonists, alpha-conotoxins are valuable tools to evaluate the functional

46 Conotoxins are venom peptides from cone snails with mult

47 To date, cone snail toxins ("conotoxins") are of great interest in the pursuit of nov

48 f a selective alpha7 nAChR antagonist, alpha-conotoxin ArIB [V11L,V16D] (ArIB) into the nucleus accum

49 This work extends the application of conotoxins as molecular probes to non-excitatory cells,

50 n and may also lead to the development of mu-conotoxins as safe analgesics.

51 alpha-Conotoxins, as nicotinic acetylcholine receptor (nAChR)

52 Finally, micro-infusion of alpha-conotoxin AuIB (10 mum) but not alpha-conotoxin MII (10

53 lpha3beta4* nAChR-selective antagonist alpha-conotoxin AuIB almost completely abolished nicotine-evok

54 alpha-Conotoxin AuIB is a selective alpha3beta4 nicotinic acet

55 alpha-Conotoxin AuIB, a potent antagonist of the alpha3beta4 n

56 crucial material for further development of conotoxin-based therapeutics.

57 T-1-family conotoxins belong to the T-superfamily and are composed

58 t these residues control access to the alpha-conotoxin binding site.

59 itive charge in this position prevents alpha-conotoxin binding.

60 We hypothesized that distinct conotoxin-binding kinetics could be exploited to develop

61 g structurally guided point mutations in the conotoxin-binding site.

62 d from the venom of cone snails, known as mu-conotoxins, block voltage-gated sodium channels by physi

63 However, the lack of solved structures of conotoxins bound to nAChRs and the large size of these p

64 alpha-Conotoxin BuIA (500 nM) blocked acetylcholine-gated curr

65 inatorial library (PS-SCL) with the alpha4/4-conotoxin BuIA framework, we discovered a highly potent

66 Alpha-conotoxin BuIA kinetically distinguishes between beta2-

67 Proline6 of alpha-conotoxin BuIA was found to be critical for nAChR select

68 Block of [3H]norepinephrine release by alpha-conotoxin BuIA, a toxin that kinetically distinguishes b

69 alpha-Conotoxin BuIA[T5A;P6O] partially blocked norepinephrine

70 M-Superfamily conotoxins can be divided into the m-1, -2, -3, and -4 b

71 reviously found in the mu-, kappaM-, and psi-conotoxins (CC-C-C-CC).

72 Although most conotoxin channel blockers function by direct binding to

73 study, we designed cyclic analogues of alpha-conotoxin CIA, a potent muscle nicotinic acetylcholine r

74 -beta) in podocytes was abolished with omega-conotoxin, cilnidipine or mitogen-activated protein kina

75 The more potent of the four new mu-conotoxins, CnIIIA and CIIIA, exhibited a strikingly dif

76 r cloning was used to identify four novel mu-conotoxins: CnIIIA, CnIIIB, CIIIA, and MIIIA from Conus

77 Conotoxins contain conserved cysteine residues that form

78 nd cannabidiol closely matched that of omega-conotoxin CVIE, a potent and selective Cav2.2 calcium ch

79 include cysteine-rich, hydrophobic peptides (conotoxins delta-SVIE and MrVIA), nodule-specific, cyste

80 al libraries in the discovery of novel alpha-conotoxin derivatives with refined pharmacological activ

81 nd generation library of 64 individual alpha-conotoxin derivatives.

82 ort a new family of four-cystine, three-loop conotoxins (designated framework 14).

83 one snail Conus planorbis, we isolated a new conotoxin, designated pl14a, with potent activity at bot

84 rise of integrated venomics has accelerated conotoxin discovery with now well over 10,000 conotoxin

85 44 toxins, respectively), as well as 208 new conotoxins displaying odd numbers of cysteine residues d

86 Previous investigations of four-loop conotoxin expression patterns of six closely related Con

87 (Most belong to the alpha- and alphaA-conotoxin families.) When administered to mice and fish

88 that includes Conus radiatus uses the alphaS-conotoxin family to target the muscle nAChR and paralyze

89 longs to the alpha4/3 subfamily of the alpha-conotoxin family; sequence and subtype specificity compa

90 These conotoxins fold into small highly structured frameworks,

91 The only previously characterized conotoxin from the S superfamily, sigma-conotoxin GVIIIA

92 We have purified and characterized a novel conotoxin from the venom of Conus obscurus, which has th

93 e purification and characterization of a new conotoxin from the venom of Conus radiatus.

94 This study describes a novel alpha-conotoxin from the Western Atlantic species Conus regius

95 dge, this is the first characterization of a conotoxin from this species.

96 roach we readily produced three native delta-conotoxins from Conus consors plus two rationally design

97 ave characterized newly identified alphaA(S)-conotoxins from Conus pergrandis and have conducted a mo

98 Structure-activity information regarding conotoxins from distantly related Conus species was empl

99 striking sequence similarity to these delta-conotoxins from piscivorous cone snail venoms.

100 ed the function of 4-hydroxyproline (Hyp) in conotoxins from three distinct gene families: mu-, omega

101 n of a complex between BiP, PDI, and nascent conotoxins further suggests that the folding and assembl

102 prior studies have specifically explored how conotoxin gene evolution contributes to the differentiat

103 ear evidence of sequence similarity with any conotoxin gene family.

104 An alpha-conotoxin gene was cloned from Conus arenatus.

105 Conotoxin GeXIVA inhibits the alpha9alpha10 nicotinic ac

106 wever, neither alpha-conotoxin MII nor alpha-conotoxin GIC at concentrations of 10 microM blocked ace

107 Here we present the structure of alpha-conotoxin GIC in complex with Aplysia californica AChBP

108 forts have been made to understand why alpha-conotoxin GIC is strongly selective for alpha3beta2 nACh

109 The Cav2.2 (N-type) blocker omega-conotoxin GVIA (1 microM) was the only blocker that sign

110 A-targeting small-interfering RNA, and omega-conotoxin GVIA (a CaV2.2 blocker) attenuated RIM1alpha u

111 unperturbed by omega-agatoxin IVA and omega-conotoxin GVIA (P/Q-type and N-type channel inhibitors,

112 Conotoxin GVIA abolished all EPSPs in inspiratory neuron

113 fects, whereas both the N-type blocker omega-conotoxin GVIa and the L-type blocker nimodipine reduced

114 wed that both the N-type Ca channel blocker -conotoxin GVIA and the P/Q-type Ca channel blocker -agat

115 iated responses, as it is blocked by a omega-conotoxin GVIA application.

116 Finally, [(125)I]Tyr22-omega-conotoxin GVIA cell surface binding in tsA201 cells stab

117 ga-IVA, but the N-type channel blocker omega-conotoxin GVIA had no effect.

118 Blocking N-type calcium channels with conotoxin GVIA had only minor effects on respiratory act

119 The N-type Ca2+ channel toxin omega-conotoxin GVIA inhibited both the [Zn]t and fEPSP equall

120 atoxin IVA or the N-channel antagonist omega-conotoxin GVIA or both.

121 Inhibiting N-type Ca(2+) channels with omega-conotoxin GVIA or omega-conotoxin MVIIC partially mimick

122 P/Q-type channel confirmed a block by omega-conotoxin GVIA raising the likelihood that all vertebrat

123 Cd(2+) or the specific N-type blocker omega-conotoxin GVIA to examine the calcium dependence of the

124 folding and the functional activity of omega-conotoxin GVIA, a well-characterized ICK-motif peptidic

125 type Ca2+ channels were inhibited with omega-conotoxin GVIA, but were not blocked when bath Ca2+ was

126 and the N-type calcium channel toxin, omega-conotoxin GVIA, each reduced the ischaemia-evoked motor

127 ive), N- and P/Q- (omega-agatoxin IVA, omega-conotoxin GVIA, omega-conotoxin MVIIC-sensitive), R- (Ni

128 t was occluded by prior application of omega-conotoxin GVIa, suggesting that a major fraction of Ca(2

129 d by nimodipine-, omega-agatoxin IVA-, omega-conotoxin GVIA- and TTA-P2-sensitive currents.

130 ted, in part, by Ca(2+) flowing throughomega-conotoxin GVIA-sensitive, class 2.2 voltage-dependent Ca

131 ular transmission is also sensitive to omega-conotoxin GVIA.

132 ally on pharmacological sensitivity to omega-conotoxin GVIA.

133 voltage-gated calcium channel blocker omega-conotoxin GVIA.

134 by the neurotoxins, tetrodotoxin, and omega-conotoxin GVIA.

135 release was blocked by tetrodotoxin or omega-conotoxin GVIA.

136 etron or the N-type Ca-channel blocker omega-Conotoxin GVIA.

137 in a blocker of N-type Ca2+ channels (omega-conotoxin GVIA; 30 nM).

138 hannel blockers omega-agatoxin-IVA and omega-conotoxin-GVIA and to metal cation blockers Cd(2+) and N

139 Omega-conotoxin-GVIA occluded the effect of ethanol on NMDA EP

140 omega-conotoxin-MVIIC inhibit, but not omega-conotoxin-GVIA), intact vesicle fusion processes (tetanu

141 ized conotoxin from the S superfamily, sigma-conotoxin GVIIIA, is a specific competitive antagonist o

142 A cone snail venom peptide, muO section sign-conotoxin GVIIJ from Conus geographus, has a unique post

143 muO section sign-conotoxin GVIIJ is a 35-aa peptide, with 7 cysteine resi

144 ght into the large, yet poorly characterized conotoxin H-superfamily, we used NMR and CD spectroscopy

145 Although several analgesic conotoxins have already reached human clinical trials, a

146 ugh potent alpha3beta2 nAChR-selective alpha-conotoxins have been identified, currently characterized

147 the m-2 branch peptide mr3a, even though the conotoxins have different disulfide connectivity pattern

148 connectivity, and previous studies of alpha-conotoxins have focused on the globular isomers as the r

149 alpha-Conotoxins have four cysteines that can have three possi

150 ranslational modifications characteristic of conotoxins (hydroxyproline, gamma-carboxyglutamate) are

151 the alpha7-nicotinic receptor blocker alpha-conotoxin ImI (alpha-ImI) with polyethylene glycol space

152 l-characterized member of this family, alpha-conotoxin ImI (alpha-ImI), which is a potent inhibitor o

153 tagenesis studies and experiments with alpha-conotoxin ImI and a chimeric Naja oxiana alpha-neurotoxi

154 alpha-Conotoxin ImI displayed inhibitory activity as well.

155 synthetic combinatorial approach using alpha-conotoxin ImI to develop potent and selective alpha(7) n

156 on the three residues of the n-loop of alpha-conotoxin ImI to give a total of 10,648 possible combina

157 o accommodate the peptidic antagonist, alpha-conotoxin ImI, but wraps around the agonists lobeline an

158 For alpha-conotoxins ImI and GI, the hydroxylation of the conserve

159 nAChR antagonists (methyllycaconitine, alpha-conotoxin-ImI) and glutamate receptor (GluR) antagonists

160 we used a number of subtype-selective alpha-conotoxins in combination with nicotinic receptor subuni

161 discuss the effects of Hyp on the folding of conotoxins in the context of cis-trans isomerization of

162 lations of homology models with docked alpha-conotoxin indicate that these residues control access to

163 transferable C-terminal postpeptide in these conotoxins indicates the presence of the gamma-carboxyla

164 ns, the N-type calcium channel blocker omega-conotoxin inhibited this spontaneous response.

165 Conotoxin iota-RXIA, from the fish-hunting species Conus

166 er suggests that the folding and assembly of conotoxins is a highly regulated multienzyme-assisted pr

167 mechanisms targeted by different classes of conotoxins is discussed.

168 with previous contradicting publications, mu-conotoxin KIIA and hepcidin-25, are included, and their

169 The analgesic mu-conotoxin KIIIA (KIIIA), a 16-residue peptide with three

170 Micro-conotoxin KIIIA is representative of micro-conopeptides

171 In the case of mu-Conotoxin KIIIA, the PADLOC connectivity (1-15,2-9,4-16)

172 We conjugated mu-conotoxin KIIIA, which occludes the pore of the Na(V) ch

173 ogies, including hepcidin, Kalata-B1, and mu-Conotoxin KIIIA.

174 d "Mini peptide." It was derived from the mu-conotoxins KIIIA and BuIIIC.

175 -dimensional solution structure of the alpha-conotoxin Lo1a was determined by NMR spectroscopy.

176 solated an 18-amino acid peptide named alpha-conotoxin Lo1a, which is active on nAChRs.

177 The asymmetric evolution of conotoxin loci among species may result from lineage-spe

178 alyze the molecular evolution of orthologous conotoxin loci of these species and specifically examine

179 selection from predator-prey interactions on conotoxin loci.

180 lective antagonists d-tubocurarine and alpha-conotoxin MI.

181 alpha-conotoxin AuIB (10 mum) but not alpha-conotoxin MII (10 mum) into the IPn in rats increased ni

182 he alpha3beta2*/alpha6beta2* selective alpha-conotoxin MII (alpha-CTX MII) dose- and time-dependently

183 In this study, we used a novel alpha-conotoxin MII (alpha-CtxMII) analog E11A to further inve

184 ls, alpha6beta2(*) nAChR blockade with alpha-conotoxin MII (alpha-CtxMII) decreased release with nonb

185 important in nicotine addiction, binds alpha-conotoxin MII (alpha-CtxMII) with high affinity and is h

186 Binding of [(125)I]alpha-conotoxin MII (largely to alpha6* nAChRs) did not system

187 Intriguingly, alpha-conotoxin MII [H9A; L15A], blocked cocaine conditioning

188 njection of the selective alpha6beta2* alpha-conotoxin MII [H9A; L15A], blocked nicotine CPP.

189 Whereas alpha-conotoxin MII fully inhibits nicotine-evoked [3H]norepin

190 However, neither alpha-conotoxin MII nor alpha-conotoxin GIC at concentrations

191 lpha3beta2* nAChR-selective antagonist alpha-conotoxin MII only partially attenuated these currents.

192 do-A-85380, sazetidine-A, varenicline, alpha-conotoxin MII, and bPiDDB (N,N-dodecane-1,12-diyl-bis-3-

193 igned and synthesized a novel analog ofalpha-conotoxin MII, MII[S4A,E11A,L15A], and tested it on nACh

194 iatal dopamine release (both total and alpha-conotoxin MII-resistant release) increased with age in n

195 oncentrations compared with mecamylamine and conotoxin MII.

196 the alpha3beta2-preferring antagonist alpha-conotoxin MII.

197 alpha-conotoxin MII[H9A;L15A] also significantly reduced the l

198 TA DAergic neurons that was blocked by alpha-conotoxin MII[H9A;L15A], a selective antagonist of nAChR

199 d several minutes and was sensitive to alpha-conotoxin MII[H9A;L15A].

200 the giant fiber system is inhibited by alpha-conotoxins MII, AuIB, BuIA, EI, PeIA, and ImI.

201 mutants revealed increased affinity of alpha-conotoxins MII, TxIA, and [A10L]TxIA at the alpha4(R185I

202 bers of cysteine residues derived from known conotoxin motifs.

203 a "triple-turn" motif seen in the m-2 branch conotoxin mr3a, which is absent in mr3e, the only other

204 The muO-conotoxins MrVIA, MrVIB, and MfVIA inhibit the voltage-g

205 MuO-conotoxin MrVIB is a blocker of voltage-gated sodium cha

206 ng and apply it to a three-disulfide-bridged conotoxin, mu-SxIIIA (from the venom of Conus striolatus

207 nnel and disrupting its normal ion movement, conotoxin muO section sign-GVIIJ channel blocking is uni

208 Disulfide exchange is possible because conotoxin muO section sign-GVIIJ contains anS-cysteinyla

209 Application of 1 microM omega-conotoxin MVIIC (a Cav2.1/2.2 blocker) broadened APs but

210 channels with omega-conotoxin GVIA or omega-conotoxin MVIIC partially mimicked apamin, while inhibit

211 n, low concentrations of tetrodotoxin, omega-conotoxin MVIIC, calcium/calmodulin-dependent protein ki

212 ga-agatoxin IVA, omega-conotoxin GVIA, omega-conotoxin MVIIC-sensitive), R- (Ni(2+) -sensitive) and T

213 ase was blocked both by nifedipine and omega-conotoxin MVIIC.

214 VDCC currents (omega-agatoxin-IVA and omega-conotoxin-MVIIC inhibit, but not omega-conotoxin-GVIA),

215 Cs in the presence of tetrodotoxin and omega-conotoxin-MVIIC, consistent with inhibition of presynapt

216 All previously characterized competitive conotoxin nAChR antagonists have been members of the A s

217 (AChRs) using a novel peptide toxin (alphaA-conotoxin OIVA[K15N]), prolongation of both EPC and MEPC

218 Although this conotoxin, alphaA-conotoxin OIVB (alphaA-OIVB), is a high-affinity antagon

219 the alpha3beta2 nAChR indicating that alpha-conotoxin OmIA in combination with the AChBP may serve a

220 alpha-Conotoxin OmIA was purified from the venom of Conus omar

221 s is expressed in the genus Conus (known as "conotoxins" or "conopeptides").

222 Alpha-conotoxin PeIA displayed a 260-fold higher selectivity f

223 Alpha-conotoxin PeIA represents a novel probe to differentiate

224 and characterization of a novel toxin alpha-conotoxin PeIA that discriminates between alpha9alpha10

225 sed positional scanning mutagenesis of alpha-conotoxin PeIA, which targets both alpha6beta2* and alph

226 novel analogs of a recently described alpha-conotoxin, PeIA.

227 2- and 3-disulfide-bonded isomers of the mu-conotoxin PIIIA were investigated for their distinguisha

228 lar dynamics, we show that one subtype of mu-conotoxins, PIIIA, effectively blocks the bacterial volt

229 segment of the helix-promoting peptide alpha-conotoxin pl14a.

230 Venom peptide toxins such as conotoxins play a critical role in the characterization

231 multimeric ligands can significantly enhance conotoxin potency and selectivity at homomeric nicotinic

232 in loop C completely transferred high alpha-conotoxin potency to the alpha4beta2 receptor.

233 Conversely, alpha-conotoxin potency was reduced at the reverse alpha3(I186

234 Native alpha-conotoxins preferably adopt the globular connectivity, a

235 d a more detailed characterization of alphaA-conotoxins previously reported from additional Conus spe

236 We used conotoxin probes together with subunit-null mice to inte

237 apital ES, CyrillichBP in complex with alpha-conotoxins provide important insights into the interacti

238 ber of ER-resident enzymes in the folding of conotoxins, providing novel insights into the enzyme-gui

239 The peptide, designated alphaC-conotoxin PrXA (alphaC-PrXA), is the defining member of

240 Here we used the alpha4/7-conotoxin RegIIA, a disulfide-bonded peptide from the ve

241 sly reported the discovery of a new alpha4/7-conotoxin, RegIIA.

242 ts, the characterization of the short alphaA-conotoxins revealed diverse kinetics of a block of the f

243 The 13-residue peptide alpha-conotoxin RgIA (alpha-RgIA) is a member of the alpha-4,3

244 Western Atlantic species Conus regius, alpha-conotoxin RgIA (alpha-RgIA), that is a subtype specific

245 alpha-Conotoxin RgIA is both an antagonist of the alpha9alpha1

246 hR antagonists, alpha-bungarotoxin and alpha-conotoxin RgIA, blocked efferent-mediated inhibition in

247 mino acid residues, a striking example being conotoxins RgIA and GeXIVA from marine mollusk venom, wi

248 this assertion by demonstrating that kappaM-conotoxin RIIIJ (kappaM-RIIIJ) from Conus radiatus preci

249 n, synthesis, and characterization of kappaM-conotoxin RIIIJ from the venom of a fish-hunting species

250 The peptide, alphaS-conotoxin RVIIIA (alphaS-RVIIIA), is biochemically uniqu

251 Whereas conotoxins selectively target specific neuronal proteins

252 onotoxin discovery with now well over 10,000 conotoxin sequences published.

253 erse among species and the genes that encode conotoxins show high rates of evolution.

254 en identified, currently characterized alpha-conotoxins show no or only weak affinity for alpha4beta2

255 ever, the alpha(1B)-AR-selective mutant F18A conotoxin showed a striking biphasic inhibition in alpha

256 This is the first conotoxin shown to affect the activity of both voltage-g

257 ignment of disulfide connectivities in alpha-conotoxin SII, of which approximately 30% of its mass is

258 tides and of the previously characterized mu-conotoxin SmIIIA (which also blocks TTX-resistant channe

259 Enzymes in this PDI family, termed conotoxin-specific PDIs, significantly and differentiall

260 ort the definition and characterization of a conotoxin subfamily, designated the short alphaA-conotox

261 es with those of previously characterized mu-conotoxins suggested that the new mu-conotoxins were lik

262 e peptides, including alpha-, mu-, and omega-conotoxins, suggesting that the integrated oxidative fol

263 ffects were seen with other alpha6-selective conotoxins, suggesting the general importance of theseal

264 The M-superfamily, one of eight major conotoxin superfamilies found in the venom of the cone s

265 In this work, the M-conotoxin superfamily is defined using both biochemical

266 14a belongs to a new gene superfamily, the J-conotoxin superfamily.

267 to be related to the K channel-targeted I(2) conotoxin superfamily.

268 ional diversities of an emerging group of mu-conotoxins targeting TTX-r sodium channels.

269 the first example of analgesia produced by a conotoxin that blocks sodium channels.

270 e isolation and characterization of an alpha-conotoxin that has the highest known affinity for the Ly

271 ammatory effect of ImI, a well characterized conotoxin that inhibits alpha7 nAChRs, on differentiated

272 of Conus brunneus, we found BruIB, an alpha-conotoxin that inhibits Drosophila nicotinic receptors b

273 The discovery of a delta-conotoxin that potently acts on vertebrate sodium channe

274 ChR antagonist; all previously characterized conotoxins that competitively antagonize nAChRs are stru

275 ) or 500 nM PnIA (23.0+/-4% blockade), alpha-conotoxins that target alpha7 and alpha3beta2*/alpha6bet

276 designed based on two naturally occurring mu-conotoxins that target Na(v)s.

277 nM BuIA[T5A;P6O] or 200 nM MII[E11A], alpha-conotoxins that target the alpha6beta4* subtype, blocked

278 s marine cone snails produce peptide toxins (conotoxins) that bind ion channels and receptors with hi

279 iology together with subtype-selective alpha-conotoxins to pharmacologically characterize the nAChRs

280 usage bias and RNA-editing processes of the conotoxin transcripts demonstrate a specific conservatio

281 This smoking gun is delta-conotoxin TsVIA, a peptide from the venom of Conus tessu

282 chanism of prey capture; this peptide, delta-conotoxin TsVIA, has striking sequence similarity to the

283 e-dimensional solution structure for the m-1 conotoxin tx3a found in the venom of Conus textile.

284 is review, we highlight the diversity of new conotoxins uncovered since 2014, their three-dimensional

285 the kinetic diversity, should make alphaA(S)-conotoxins useful ligands for a diverse set of studies.

286 physiology, and mutagenesis, we showed alpha-conotoxin Vc1.1 modulates Cav2.2 via a different pathway

287 alpha-Conotoxin Vc1.1 specifically and potently inhibits the n

288 Analgesic alpha-conotoxin Vc1.1, a peptide from predatory marine cone sn

289 es, including the cyclotide kalata B1, alpha-conotoxin Vc1.1, and sunflower trypsin inhibitor 1.

290 alpha-Conotoxins Vc1.1 and RgIA are small peptides isolated fr

291 ct of the GABA(B) agonist baclofen and alpha-conotoxins Vc1.1 and RgIA on calcium channel currents af

292 a(v)2.2) calcium channels by analgesic alpha-conotoxins Vc1.1 and RgIA.

293 One of these conotoxins (vil14a) has a Lys/Tyr dyad, separated by app

294 thways can be selectively inhibited by alpha-conotoxins; we show that in the model organism Drosophil

295 ized mu-conotoxins suggested that the new mu-conotoxins were likely to target tetrodotoxin-resistant

296 h diversity of toxins in their venom such as conotoxins, which are short polypeptides stabilized by d

297 The ligand is the first alpha-conotoxin with higher affinity for the closely related r

298 tant insights into the interactions of alpha-conotoxins with distinct nAChR subtypes.

299 g folding, improving yields, and stabilizing conotoxins with therapeutic potential.

300 peptides based on known pharmacophores of mu-conotoxins without losing their potency and selectivity.