A novel 4/6-type alpha-conotoxin ViIA selectively inhibits nAchR &amp;alpha;3&amp;beta;2 subtype

Li, Liang; Liu, Na; Ding, Rong; Wang, Shuo; Liu, Zhuguo; Li, Haiying; Zheng, Xiaohui; Dai, Qiuyun

doi:10.1093/abbs/gmv105

Cited by 7 publications

(10 citation statements)

References 39 publications

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“…weight (Da) Cys. framework Conotoxin superfamily and family Molecular function Reference Kappa-ViTX MMFRLTSVSCFLLVIACLNLFQVVLTSRCFPPGIYCTPYLPCCWGICCGTCRNVCHLRIGKRATFQE 67 7,599 XI (C-C-CC-CC-C-C) (I2) S.Family κ-Conotoxin Impairing of VG-K + ion channels [ 50 ] Alpha-ViIA MGMRMMFVVFLLVVFASSVTLDRASYGRYASPVDRASALIAQAILRDCCSNPPCAHNNPDCR 62 6,810 I (CC-C-C) (A) S.Family α-Conotoxin Inhibiting nAChR [ 51 ] Contryphan-Vi MGKLTILVLVAAVLLSTQVMVQGDGDQPADRNAVRRDDNPGGLSGKFMNVLRRSGCPWHPWCG 63 6,806 C-C (O2) S.Family Contryphan Family Impairing VG-Ca 2+ and KCa channels [ 52 ">] ViVA MRCVPVFIILLLLIPSASSAAVQPKTEKDDVPLASVHDSALRILSRQCCITIPECCRIG 59 6,393 V (CC-CC) (T) S.Family Unknown [ 53 ] ViVB MRCVPVFIILLLLIPSAPSAAVQPKTEKDDVPLASFHDSAMRILSRQCCPTIPECCRVG 59 6,439 V (CC-CC) (T) S.Family Unknown [ 53 ] …”

Section: Discussionmentioning

confidence: 99%

Prospecting for candidate molecules from Conus virgo toxins to develop new biopharmaceuticals

Mohamed

Nabil

El-Naggar

2022

J. Venom. Anim. Toxins incl. Trop. Dis

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Background A combination of pharmacological and biomedical assays was applied in this study to examine the bioactivity of Conus virgo crude venom in order to determine the potential pharmacological benefit of this venom, and its in vivo mechanism of action. Methods Two doses (1/5 and 1/10 of LC 50 , 9.14 and 4.57 mg/kg) of the venom were used in pharmacological assays (central and peripheral analgesic, anti-inflammatory and antipyretic), while 1/2 of LC 50 (22.85 mg/kg) was used in cytotoxic assays on experimental animals at different time intervals, and then compared with control and reference drug groups. Results The tail immersion time was significantly increased in venom-treated mice compared with the control group. Also, a significant reduction in writhing movement was recorded after injection of both venom doses compared with the control group. In addition, only the high venom concentration has a mild anti-inflammatory effect at the late inflammation stage. The induced pyrexia was also decreased significantly after treatment with both venom doses. On the other hand, significant increases were observed in lipid peroxidation (after 4 hours) and reduced glutathione contents and glutathione peroxidase activity, while contents of lipid peroxidation and nitric oxide (after 24 hours) and catalase activity were depleted significantly after venom administration. Conclusion These results indicated that the crude venom of Conus virgo probably contain bioactive components that have pharmacological activities with low cytotoxic effects. Therefore, it may comprise a potential lead compound for the development of drugs that would control pain and pyrexia.

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Section: Discussionmentioning

confidence: 99%

Prospecting for candidate molecules from Conus virgo toxins to develop new biopharmaceuticals

Mohamed

Nabil

El-Naggar

2022

J. Venom. Anim. Toxins incl. Trop. Dis

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“…The venom ducts were dissected from living cone snails and frozen immediately in liquid nitrogen. Total RNA was extracted and purified from ~100 mg of homogenized venom duct tissue using TRIZOL Reagent (Invitrogen, Carlsbad, CA, USA) as described previously 42 , 43 .…”

Section: Methodsmentioning

confidence: 99%

A novel α-conopeptide Eu1.6 inhibits N-type (CaV2.2) calcium channels and exhibits potent analgesic activity

Liu¹,

Bartels

Sadeghi

et al. 2018

Sci Rep

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We here describe a novel α-conopeptide, Eu1.6 from Conus eburneus, which exhibits strong anti-nociceptive activity by an unexpected mechanism of action. Unlike other α-conopeptides that largely target nicotinic acetylcholine receptors (nAChRs), Eu1.6 displayed only weak inhibitory activity at the α3β4 and α7 nAChR subtypes and TTX-resistant sodium channels, and no activity at TTX-sensitive sodium channels in rat dorsal root ganglion (DRG) neurons, or opiate receptors, VR1, KCNQ1, L- and T-type calcium channels expressed in HEK293 cells. However, Eu1.6 inhibited high voltage-activated N-type calcium channel currents in isolated mouse DRG neurons which was independent of GABAB receptor activation. In HEK293 cells expressing CaV2.2 channels alone, Eu1.6 reversibly inhibited depolarization-activated Ba2+ currents in a voltage- and state-dependent manner. Inhibition of CaV2.2 by Eu1.6 was concentration-dependent (IC50 ~1 nM). Significantly, systemic administration of Eu1.6 at doses of 2.5–5.0 μg/kg exhibited potent analgesic activities in rat partial sciatic nerve injury and chronic constriction injury pain models. Furthermore, Eu1.6 had no significant side-effect on spontaneous locomotor activity, cardiac and respiratory function, and drug dependence in mice. These findings suggest α-conopeptide Eu1.6 is a potent analgesic for the treatment of neuropathic and chronic pain and opens a novel option for future analgesic drug design.

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“…A few novel conotoxins from the 4/6-group have also been characterized recently. Thus, α-conotoxin ViIA, identified in the cDNA library of the C. virgo venom duct, showed moderate affinity (IC 50 845.5 nM) only to α3β2 nAChR [ 137 ]. Another α-conotoxin, TxID, from the same group (see Figure 3 ), revealed high selectivity to α3β4 receptor (IC 50 12.5 nM), a rare selectivity as compared to other α-conotoxins [ 135 ].…”

Section: Marine Origin Peptides Targeting Nachrsmentioning

confidence: 99%

Marine Origin Ligands of Nicotinic Receptors: Low Molecular Compounds, Peptides and Proteins for Fundamental Research and Practical Applications

et al. 2022

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The purpose of our review is to briefly show what different compounds of marine origin, from low molecular weight ones to peptides and proteins, offer for understanding the structure and mechanism of action of nicotinic acetylcholine receptors (nAChRs) and for finding novel drugs to combat the diseases where nAChRs may be involved. The importance of the mentioned classes of ligands has changed with time; a protein from the marine snake venom was the first excellent tool to characterize the muscle-type nAChRs from the electric ray, while at present, muscle and α7 receptors are labeled with the radioactive or fluorescent derivatives prepared from α-bungarotoxin isolated from the many-banded krait. The most sophisticated instruments to distinguish muscle from neuronal nAChRs, and especially distinct subtypes within the latter, are α-conotoxins. Such information is crucial for fundamental studies on the nAChR revealing the properties of their orthosteric and allosteric binding sites and mechanisms of the channel opening and closure. Similar data are provided by low-molecular weight compounds of marine origin, but here the main purpose is drug design. In our review we tried to show what has been obtained in the last decade when the listed classes of compounds were used in the nAChR research, applying computer modeling, synthetic analogues and receptor mutants, X-ray and electron-microscopy analyses of complexes with the nAChRs, and their models which are acetylcholine-binding proteins and heterologously-expressed ligand-binding domains.

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A novel 4/6-type alpha-conotoxin ViIA selectively inhibits nAchR α3β2 subtype

Cited by 7 publications

References 39 publications

Prospecting for candidate molecules from Conus virgo toxins to develop new biopharmaceuticals

Prospecting for candidate molecules from Conus virgo toxins to develop new biopharmaceuticals

A novel α-conopeptide Eu1.6 inhibits N-type (CaV2.2) calcium channels and exhibits potent analgesic activity

Marine Origin Ligands of Nicotinic Receptors: Low Molecular Compounds, Peptides and Proteins for Fundamental Research and Practical Applications

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