ライフサイエンスコーパス: conotoxin

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

2 carboxylation but is not found on the mature conotoxin.

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

4 n of the Ca(v)2.2 channel by analgesic alpha-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 etics of disulfide-bond formation of several conotoxins.

9 14a and the second loop of a number of alpha-conotoxins.

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

11 d invertebrate ion channel blockers known as conotoxins.

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

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

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

15 hly helical secondary structure for the four conotoxins.

16 erlying the Nav subtype selectivity of delta-conotoxins.

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

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

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

20 sight into the "evolutionary engineering" of conotoxin activity.

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

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

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

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

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

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

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

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

29 Significantly, with more structures of alpha-conotoxins also becoming available this enables ready co

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

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

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

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

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

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

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

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

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

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

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

41 alpha-Conotoxins are peptide neurotoxins isolated from venomou

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

43 mu-Conotoxins are peptides that block sodium channels.

44 alpha-Conotoxins are selective antagonists of neuromuscular or

45 Alpha-conotoxins are small disulfide-constrained peptides from

46 alpha-Conotoxins are subtype-selective nicotinic acetylcholine

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

48 Conotoxins are venom peptides from cone snails with mult

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

50 om venoms of predatory marine Conus snails ("conotoxins") are well-known to be highly potent and sele

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

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

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

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

55 alpha-Conotoxin AuIB is a selective alpha3beta4 nicotinic acet

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

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

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

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

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

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

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

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

81 CD spectra and nanoNMR spectroscopy of these conotoxins directly isolated from the cone snails reveal

82 44 toxins, respectively), as well as 208 new conotoxins displaying odd numbers of cysteine residues d

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

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

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

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

87 These conotoxins fold into small highly structured frameworks,

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

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

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

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

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

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

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

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

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

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

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

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

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

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

102 Conotoxin GeXIVA inhibits the alpha9alpha10 nicotinic ac

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

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

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

106 two novel gamma-carboxyglutamate-containing conotoxins, Gla-TxX and Gla-TxXI, from the venom of Conu

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

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

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

110 Conotoxin GVIA abolished all EPSPs in inspiratory neuron

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

132 ally on pharmacological sensitivity to omega-conotoxin GVIA.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

148 alpha-Conotoxin ImI displayed inhibitory activity as well.

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

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

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

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

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

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

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

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

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

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

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

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

161 mechanisms targeted by different classes of conotoxins is discussed.

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

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

164 Micro-conotoxin KIIIA is representative of micro-conopeptides

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

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

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

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

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

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

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

172 selection from predator-prey interactions on conotoxin loci.

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

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

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

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

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

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

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

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

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

182 binding of either labeled Epb or 125I-alpha-conotoxin MII increased to a much greater extent than di

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

184 Alpha-conotoxin MII, a peptide toxin isolated from Conus magus

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

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

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

188 the alpha3beta2-preferring antagonist alpha-conotoxin MII.

189 oncentrations compared with mecamylamine and conotoxin MII.

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

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

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

193 notoxin PeIA bears high resemblance to alpha-conotoxins MII and GIC isolated from Conus magus and Con

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

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

196 ) = 1.2 microM) that was unaffected by alpha-conotoxin-MII or dihydro-beta-erythroidine, antagonists

197 ical characterization of one peptide, kappaA-conotoxin MIVA is reported; five of the other predicted

198 bers of cysteine residues derived from known conotoxin motifs.

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

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

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

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

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

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

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

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

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

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

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

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

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

212 As such, alpha-conotoxins offer the potential to become templates for t

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

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

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

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

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

218 Alpha-conotoxin PeIA bears high resemblance to alpha-conotoxin

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

220 Alpha-conotoxin PeIA represents a novel probe to differentiate

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

222 lpha-bungarotoxin-sensitive receptors, alpha-conotoxin PeIA was also active at alpha3beta2 receptors

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

240 well as those encoding mu-, kappaM-, and psi-conotoxins revealed highly conserved amino acid residues

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

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

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

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

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

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

247 Whereas conotoxins selectively target specific neuronal proteins

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

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

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

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

252 alpha-Conotoxin SII was shown to possess 3-8, 2-18, and 4-14 d

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

254 el TTX-resistant sodium channel blockers, mu-conotoxins SIIIA and KIIIA, from two species of cone sna

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

256 ructural and functional differences among mu-conotoxins SmIIIA, SIIIA, and KIIIA offer a unique insig

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

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

259 f the postpeptides to propeptides from other conotoxins suggested some common elements, and amino aci

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

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

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

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

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

265 14a belongs to a new gene superfamily, the J-conotoxin superfamily.

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

267 defines a gene superfamily, designated the M-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 structurally and pharmacologically distinct conotoxins that are particularly prominent in the venoms

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

295 IVA is reported; five of the other predicted conotoxins were previously venom-purified.

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.