Pharmacological characterization of conotoxin lt14a as a potent non-addictive analgesic

Ren, Zhenghua; Wang, Lei; Qin, Mengying; You, Yuwen; Pan, Wuguang; Zhou, Liang; Sun, Dandan; Xu, Anlong

doi:10.1016/j.toxicon.2015.01.013

Cited by 8 publications

(10 citation statements)

References 49 publications

(58 reference statements)

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“…Analgesic peptides derived from animal venom have shown potential activities by selectively acting on many molecular targets, including Nv1.7 ion channels , acid‐sensing ion channels , nAChR receptors , opioid and cannabinoid systems , Kv 4.2 ion channels , and TRPV1 ion channels . However, the analgesic mechanism or target of SsmTX‐I in this research is still not known.…”

Section: Discussionmentioning

confidence: 92%

Centipede venom peptide SsmTX-I with two intramolecular disulfide bonds shows analgesic activities in animal models

Wang

et al. 2017

J. Pept. Sci.

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Pain is a major symptom of many diseases and results in enormous pressures on human body or society. Currently, clinically used analgesic drugs, including opioids and nonsteroidal anti-inflammatory drugs, have adverse reactions, and thus, the development of new types of analgesic drug candidates is urgently needed. Animal venom peptides have proven to have potential as new types of analgesic medicine. In this research, we describe the isolation and characterization of an analgesic peptide from the crude venom of centipede, Scolopendra subspinipes mutilans. The amino acid sequence of this peptide was identical with SsmTX-I that was previously reported as a specific Kv2.1 ion channel blocker. Our results revealed that SsmTX-I was produced by posttranslational processing of a 73-residue prepropeptide. The intramolecular disulfide bridge motifs of SsmTX-I was Cys1-Cys3 and Cys2-Cys4. Functional assay revealed that SsmTX-I showed potential analgesic activities in formalin-induced paw licking, thermal pain, and acetic acid-induced abdominal writhing mice models. Our research provides the first report of cDNA sequences, disulfide motif, successful synthesis, and analgesic potential of SsmTX-I for the development of pain-killing drugs. It indicates that centipede peptide toxins could be a treasure trove for the search of novel analgesic drug candidates. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 92%

Centipede venom peptide SsmTX-I with two intramolecular disulfide bonds shows analgesic activities in animal models

Wang

et al. 2017

J. Pept. Sci.

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“…α-Conotoxin Lt020 (LtIA), a member of the α4/7 subfamily, showed high levels of expression with the average value of FPKM being ranked first in the three C. litteratus groups (Table 5), and has been characterized as a potent antagonist of α3β2 nAChR subtype in our lab before [33]. Lt033 (LtXIVA) belongs to the L superfamily, with FPKM ranked 6th, and has been identified as an antinociceptive agent that targets the nAChR receptor [40]. Lt072 (LtVd), the 4th-ranked FPKM, can block tetrodotoxin-sensitive (TTX-S) Na + channels [41].…”

Section: Discussionmentioning

confidence: 99%

Diversity of Conopeptides and Their Precursor Genes of Conus Litteratus

Chen

Zhangsun

et al. 2020

Marine Drugs

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The venom of various Conus species is composed of a rich variety of unique bioactive peptides, commonly referred to as conotoxins (conopeptides). Most conopeptides have specific receptors or ion channels as physiologically relevant targets. In this paper, high-throughput transcriptome sequencing was performed to analyze putative conotoxin transcripts from the venom duct of a vermivorous cone snail species, Conus litteratus native to the South China Sea. A total of 128 putative conotoxins were identified, most of them belonging to 22 known superfamilies, with 43 conotoxins being regarded as belonging to new superfamilies. Notably, the M superfamily was the most abundant in conotoxins among the known superfamilies. A total of 15 known cysteine frameworks were also described. The largest proportion of cysteine frameworks were VI/VII (C-C-CC-C-C), IX (C-C-C-C-C-C) and XIV (C-C-C-C). In addition, five novel cysteine patterns were also discovered. Simple sequence repeat detection results showed that di-nucleotide was the major type of repetition, and the codon usage bias results indicated that the codon usage bias of the conotoxin genes was weak, but the M, O1, O2 superfamilies differed in codon preference. Gene cloning indicated that there was no intron in conotoxins of the B1- or J superfamily, one intron with 1273–1339 bp existed in a mature region of the F superfamily, which is different from the previously reported gene structure of conotoxins from other superfamilies. This study will enhance our understanding of conotoxin diversity, and the new conotoxins discovered in this paper will provide more potential candidates for the development of pharmacological probes and marine peptide drugs.

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“…The C. litteratus peptide has recently been reported to target neuronal nicotinic acetylcholine receptors and participate in the nAChR pathway with Ca 2+ signaling. Lt14a suppresses intracellular Ca 2+ i by blocking nAChR [ 36 ]. Ca 2+ signaling is a vital pathway in T. gondii , in which there is a correlation between Ca 2+ concentration and virulence traits [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Effect of the Synthetic cal14.1a Conotoxin, Derived from Conus californicus, on the Human Parasite Toxoplasma gondii

et al. 2016

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Toxins that are secreted by cone snails are small peptides that are used to treat several diseases. However, their effects on parasites with human and veterinary significance are unknown. Toxoplasma gondii is an opportunistic parasite that affects approximately 30% of the world’s population and can be lethal in immunologically compromised individuals. The conventional treatment for this parasitic infection has remained the same since the 1950s, and its efficacy is limited to the acute phase of infection. These findings have necessitated the search for new drugs that specifically target T. gondii. We examined the effects of the synthetic toxin cal14.1a (s-cal14.1a) from C. californicus on the tachyzoite form of T. gondii. Our results indicate that, at micromolar concentrations, s-cal14.1a lowers viability and inhibits host cell invasion (by 50% and 61%, respectively) on exposure to extracellular parasites. Further, intracellular replication decreased significantly while viability of the host cell was unaffected. Our study is the first report on the antiparasitic activity of a synthetic toxin of C. californicus.

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Pharmacological characterization of conotoxin lt14a as a potent non-addictive analgesic

Cited by 8 publications

References 49 publications

Centipede venom peptide SsmTX-I with two intramolecular disulfide bonds shows analgesic activities in animal models

Centipede venom peptide SsmTX-I with two intramolecular disulfide bonds shows analgesic activities in animal models

Diversity of Conopeptides and Their Precursor Genes of Conus Litteratus

In Vitro Effect of the Synthetic cal14.1a Conotoxin, Derived from Conus californicus, on the Human Parasite Toxoplasma gondii

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