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Noninvasive detection of glucose (NGD) is important because ∼10% of the global population is suffering from diabetes. Herein, a three-dimensional (3D) micro-/mesoporous structure, i.e., a CoNi-N nanosheet-coated GaN 3D scaffold (CoNi-N@GaN-3S), was proposed for detecting saliva glucose, where the GaN scaffold can provide a large open surface for nanosheet decoration, while the catalytic nanosheets can increase the surface area and prevent the GaN-3S from anodic corrosion. Moreover, it was found that high-temperature ammoniation of CoNi can lead to dense atomic holes and an N-terminated surface (CoNi-N), which promoted the ionization of CoNi with a higher catalytic activity. It is the first time that dense atomic holes have been observed in CoNi to our knowledge. The designed CoNi-N@GaN-3S sensor was applied to the electrochemical detection of glucose with a low limit of detection (LOD) of 60 nM and a high sensitivity, selectivity, and stability. In addition, detection of human-saliva glucose was realized with an LOD of 5 μM, which was more than 4-fold lower than reported reliable LODs. An integrated sensor with a low consumption of saliva sample was demonstrated for NGD.

In this study, a series of one-dimensional (1D)/two-dimensional (2D) heterostructure hybrids were fabricated through the in situ growth of a Co and Ni bimetallic zeolitic imidazolate framework (CoNi-ZIF) around N-doped carbon nanotubes (N-CNTs). The hybrids were further exploited as effective supercapacitor materials. The N-CNTs were prepared by carbonizing a mixture of glucose and the melamine–cyanuric acid complex at a high temperature (900 °C) under N2 atmosphere and applied as the template for the in situ synthesis of CoNi-ZIF nanosheets (NSs). The 1D N-CNTs in the hybrids can act as the high-way for charge transfer to boost the faradaic reactions. Changing the usage of metal precursors not only provided abundant redox reaction sites in 2D CoNi-ZIF NSs but also modulated the microstructures and chemical components of the hybrids. The integration of the features of N-CNTs and CoNi-ZIF NSs can result in a synergistic effect between N-CNTs and CoNi-ZIF NSs. Therefore, the obtained CoNi-ZIFs and N-CNTs hybrid (CoNi-ZIF@N-CNT) exhibited superior electrochemical capacitive performance. Comparison revealed that theCoNi-ZIF@N-CNT-2 hybrid, which was prepared with a 1:1 mass ratio of Co(NO3)2·6H2O and Ni(NO3)2·6H2O, displayed the largest specific capacitance of 1118 F g−1 at 1 A g−1, which was higher than the capacitance of most reported metal–organic framework (MOF)-based supercapacitor electrodes. Moreover, the asymmetric supercapacitor based on the CoNi-ZIF@N-CNT-2 electrode exhibited a high energy density of 51.1 Wh kg−1 at the power density of 860.1 W kg−1 and good cycle stability. This work can provide a facile and effective way for the fabrication of heterostructured 1D/2D nanostructures based on 2D MOFs for advanced energy storage.

Animal venoms are a rich source of pharmacological compounds with ecological and evolutionary significance, as well as with therapeutic and biotechnological potentials. Among the most promising venomous animals, cone snails produce potent neurotoxic venom to facilitate prey capture and defend against aggressors.

The marine cone snail produces one of the fastest prey strikes in the animal kingdom. It injects highly efficacious venom, often causing prey paralysis and death within seconds. Each snail has hundreds of conotoxins, which serve as a source for discovering and utilizing novel analgesic peptide therapeutics. In this study, we discovered, isolated, and synthesized a novel α3/5-conotoxins derived from the milked venom of

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels widely distributed in the central peripheral nervous system and muscles which participate in rapid synaptic transmission. The α9α10 nAChR is an acetylcholine receptor subtype and is involved in chronic pain. In the present study, a new A-superfamily conotoxin Bt14.12 cloned from

α-Conotoxins are small disulfide-rich peptides found in the venom of marine cone snails and are potent antagonists of nicotinic acetylcholine receptors (nAChRs). They are valuable pharmacological tools and have potential therapeutic applications for the treatment of chronic pain or neurological diseases and disorders. In the present study, we synthesized and functionally characterized a novel α-conotoxin Bt1.8, which was cloned from Conus betulinus. Bt1.8 selectively inhibited ACh-evoked currents in Xenopus oocytes expressing rat(r) α6/α3β2β3 and rα3β2 nAChRs with an IC50 of 2.1 nM and 9.4 nM, respectively, and similar potency for human (h) α6/α3β2β3 and hα3β2 nAChRs. Additionally, Bt1.8 had higher binding affinity with a slower dissociation rate for the rα6/α3β2β3 subtype compared to rα3β2. The amino acid sequence of Bt1.8 is significantly different from other reported α-conotoxins targeting the two nAChR subtypes. Further Alanine scanning analyses demonstrated that residues Ile9, Leu10, Asn11, Asn12 and Asn14 are critical for its inhibitory activity at the α6/α3β2β3 and α3β2 subtypes. Moreover, the NMR structure of Bt1.8 indicated the presence of a relatively larger hydrophobic zone than other α4/7-conotoxins which may explain its potent inhibition at α6/α3β2β3 nAChRs.

Conotoxins constitute a treasury of drug resources and have attracted widespread attention. In order to explore biological candidates from the marine cone snail, we isolated and identified three novel conopeptides named as Vi14b, Vi002, Vi003, three conotoxin variants named as Mr3d.1, Mr3e.1, Tx3a.1, and three known conotoxins (Vi15a, Mr3.8 and TCP) from crude venoms of

Venoms of predatory marine cone snails are intensely studied because of the biomedical applications of the neuropeptides that they contain, termed conotoxins. Meanwhile some gastropod lineages have independently acquired secretory glands strikingly similar to the venom gland of cone snails, suggesting that they possess similar venoms. Here we focus on the most diversified of these clades, the genus

Herein, a signal amplified electrochemical immunosensor for the sensitive detection of cytokeratin 19 fragments (CYFRA 21-1) in human serum was discussed. The CoNi-RGO was used as a substrate for the sensor with excellent specific surface area and strong electrical conductivity, which enables more efficient attachment of antibodies. The introduction of the bimetallic sulfide NiCo

Neuronal nicotinic acetylcholine receptors (nAChRs) are important ion channel membrane proteins that are widely distributed in the central nervous system (CNS) and peripheral nervous system (PNS). As an important member, α3β4 nAChRs are related to pain sensation in PNS and nicotine addiction in CNS. However, research related to the α3β4 nAChRs is greatly limited by the lack of subtype-selective pharmacological tools. The α-conotoxin (α-CTx) TxID from the marine cone snail, Conus textile, is a selective α3β4 nAChR antagonist with relatively high potency. In this study, a fluorescent dye (5-TAMRA SE) was used to label TxID on the N-terminus of α-CTx TxID, and pure TxID-F (fluorescent analogue of TxID) was obtained by HPLC. At the same time, the potency and selectivity of TxID-F were detected by high-performance liquid chromatography (HPLC). Additionally, the potency and selectivity of TxID-F were determined by using a two-electrode voltage-clamp technique on various nAChRs expressed in the Xenopus oocyte expression system. The results obtained by electrophysiology showed that TxID-F maintained the same order of potency (IC50 73 nM) as the native toxin (IC50 25 nM) for the α3β4 nAChR subtype. In addition, the results of fluorescent spectroscopy and circular dichroism showed TxID-F has the same fluorescence as 5-TAMRA SE, as well as similar profiles as TxID. The results of flow cytometry showed that the histogram shifted significantly to the right for the RAW264.7 cells expressing α3β4-containing nAChRs stained with TxID-F and confirmed by live cell imaging. The study of fluorescent-labeled α-CTx TxID provides a rich pharmacological tool to explore the structure–function relationship, distribution, and ligand-binding domain of α3β4 nAChR subtype in the future.

Developing highly efficient, stable, recyclable, and application value heterogeneous catalysts in advanced oxidation processes has essential application value in the degradation of refractory pollutants. In this paper, the CoNi alloy anchored onto N-doped porous carbon (CoNi-600@NC) catalyst was prepared using bimetallic doped metal-organic frameworks as precursors. The magnetic CoNi-600@NC can activate peroxymonosulfate (PMS) to degrade sulfamethoxazole (SMX). Therefore, SMX can be removed 100% within 25 min. CoNi-600@NC/PMS has a broad pH (3-9) application range, good applicability, and repeatability. Radical quenching, quantitative and electrochemical experiments proved that the degradation of SMX was dominated by free radical (Superoxide anions) and non-free radical pathways (surface-bound radicals). Mechanistic analysis showed that the interaction between Co-N

Exploiting directional electron transfer cascades could lead to high-performance electrocatalysts for processes such as the hydrogen evolution reaction, but realising such systems is difficult. Herein, a hierarchical confined material (CoNi/Ru@C) is presented, which provides a suitable spatial junction to enable directional electron transfer, giving superior hydrogen evolution in alkaline water/seawater.

We isolated a new dimeric conotoxin with inhibitory activity against neuronal nicotinic acetylcholine receptors. Edman degradation and transcriptomic studies indicate a homodimeric conotoxin composed by two chains of 47 amino acid in length. It has the cysteine framework XX and 10 disulfide bonds. According to conotoxin nomenclature, it has been named as αD-FrXXA. The αD-FrXXA conotoxin inhibited the ACh-induced response on nAChR with a IC

Conotoxin sr5a had previously been identified in the vermivorous cone snail Conus spurius. This conotoxin is a highly hydrophobic peptide, with the sequence IINWCCLIFYQCC, which has a cysteine pattern "CC-CC" belonging to the T-1 superfamily. It is well known that this superfamily binds to molecular targets such as calcium channels, G protein-coupled receptors (GPCR), and neuronal nicotinic acetylcholine receptors (nAChR) and exerts an effect mainly in the central nervous system. However, its effects on other molecular targets are not yet defined, suggesting the potential of newly relevant molecular interactions. To find and demonstrate a potential molecular target for conotoxin sr5a electrophysiological assays were performed on three subtypes of voltage-activated sodium channels (Na

Fenzan, William J., Dublanka, Mario, Curth, Stefan (2022): Rediscovery of the Conus conspersus Reeve, 1844 holotype. Zootaxa 5154 (4): 496-500, DOI: https://doi.org/10.11646/zootaxa.5154.4.7

BACKGROUND: Marine animals have been considered by many researchers due to their various pharmacological effects. One group of marine animals that have been studied is cone snails. The conotoxin obtained from these marine animals has various therapeutic effects. METHODS: This study was designed to investigate the apoptotic effects of crude venom of Conus textile and its fractions (A and B) on chronic lymphocytic leukemia (CLL) cells. Accordingly, parameters such as cell viability, reactive oxygen species (ROS) level, collapse in mitochondrial membrane potential (MMP), lysosomal membrane damage and caspase-3 activation were evaluated. RESULTS: The results showed that the crude venom (50, 100 and 200 µg/ml) from Conus textile and its fraction B (50, 100 and 200 µg/ml) significantly reduced viability in CLL B-lymphocyte. In addition, exposure of CLL B-lymphocyte to fraction B (50, 100 and 200 µg/ml) was associated with an increase in the level of ROS, the collapse of the MMP, damage to the lysosomal membrane, and activation of caspase-3. CONCLUSION: According to results, it was concluded that fraction B from crude venom of Conus textile causes selective toxicity on CLL B-lymphocyte with almost no effect on a normal lymphocyte. Furthermore, this venom fraction could be a promising candidate for induction of apoptosis in patients with CLL through the mitochondrial pathway.

Cone snails are predatory gastropod mollusks that are distributed in all tropical marine environments and contain small peptides (conotoxins) in their venom to capture prey. However, the biochemical and molecular aspects of conotoxins remain poorly understood. In this article, a novel α4/7-conotoxin, Lv1d, was obtained from the venom duct cDNA library of the worm-hunting Conus lividus collected from the South China Sea. The cDNA of Lv1c encodes a 65 residue conopeptide precursor, which consists of a 21 residue signal peptide, a 27 residue Pro region, and 17 residues of mature peptide. The mature peptide Lv1d was chemically synthesized according to the sequence GCCSDPPCRHKHQDLCG. It was found that 10 μM Lv1d can completely inhibit frog sciatic nerve-gastrocnemius muscle contractility within 60 min. Moreover, 100 μg/kg Lv1d showed good analgesic effects in mouse hot plate model and formalin test. Patch clamp experiments showed that 5 μM Lv1d can inhibit the cholinergic microexcitatory postsynaptic currents (mEPSCs) requency and amplitude of projection neurons in Drosophila. In conclusion, the synthesis of Lv1d and its biological and physiological data might contribute to the development of this peptide as a novel potential drug for therapeutic applications. This finding also expands the knowledge of the targeting mechanism of the α4/7-subfamily conotoxins.

Several Conus-derived venom peptides are promising lead compounds for the management of neuropathic pain, with α-conotoxins being of particular interest. Modification of the interlocked disulfide framework of α-conotoxin Vc1.1 has been achieved using on-resin alkyne metathesis. Although introduction of a metabolically stable alkyne motif significantly disrupts backbone topography, the structural modification generates a potent and selective GABAB receptor agonist that inhibits Cav2.2 channels and exhibits dose-dependent reversal of mechanical allodynia in a behavioral rat model of neuropathic pain. The findings herein support the hypothesis that analgesia can be achieved via activation of GABABRs expressed in dorsal root ganglion (DRG) sensory neurons.

My path to research in neuropharmacology has been a coalescing of my training as a molecular biologist and my intense interest in an esoteric group of animals, the fish-hunting cone snails. Attempting to bridge these two disparate worlds has led me to an idiosyncratic career as a pharmacologist.

Somatostatin (SS) is a peptide hormone with diverse physiological roles. By investigating a deep-water clade of fish-hunting cone snails, we show that predator-prey evolution has generated a diverse set of SS analogs, each optimized to elicit specific systemic physiological effects in prey. The increased metabolic stability, distinct SS receptor activation profiles, and chemical diversity of the venom analogs make them suitable leads for therapeutic application, including pain, cancer, and endocrine disorders. Our findings not only establish the existence of SS-like peptides in animal venoms but also serve as a model for the synergy gained from combining molecular phylogenetics and behavioral observations to optimize the discovery of natural products with biomedical potential.

Dermal sinus is more commonly associated with intradural dermoid than an epidermoid cyst. Conus epidermoid cyst with dermal sinus is a rare entity. We are presenting a rare case of infected conus epidermoid cyst along with the dermal sinus in an 18-month-old girl presented with flaccid paraparesis with sphincter dysfunction and timely intervention leads to complete recovery. We had searched PubMed for previously reported similar cases and did a case-based review of the literature. This 18-month-old girl with discharging lumbosacral sinus with fever since 3 days presented with flaccid paraparesis with sphincter dysfunction. Preoperative magnetic resonance imaging (MRI) showed a large enhancing lesion from L1-S1 along with the dermal sinus tract. Complete excision of the cyst along with the sinus tract, followed by long-term antibiotic therapy. The excision of the infected cyst was done through myelotomy under neuromonitoring, while some part of the capsule densely adherent to the neural tissue was left behind. The patient gradually improved following surgery and motor power of the lower limbs were $$ \raisebox{1ex}{$3$}\!\left/ \!\raisebox{-1ex}{$5$}\right. $$ while going home. Histopathology revealed epidermoid cyst with secondary inflammatory tissue. Follow-up MRI of the spine showed excision of the dermal sinus tract and cyst with postoperative changes. At 1-year follow-up, the patient was asymptomatic without any focal deficits. Early surgical intervention followed by long-term antibiotic therapy is a must for good functional recovery in patients of an infected dermal sinus tract with associated cyst. While excising cyst through myelotomy, some part of the capsule densely adherent to neural tissue may be left behind. Regular follow-up in the first year of surgery is essential to look for the recurrence of the lesion.

Conotoxins (CnTX) are bioactive peptides produced by marine molluscs belonging to Conus genus. The biochemical structure of these venomous peptides is characterized by a low number of amino acids linked with disulfide bonds formed by a high degree of post-translational modifications and glycosylation steps which increase the diversity and rate of evolution of these molecules. CnTX different isoforms are known to target ion channels and, in particular, voltage-gated sodium (Na+) channels (Nav channels). These are transmembrane proteins fundamental in excitable cells for generating the depolarization of plasma membrane potential known as action potential which propagates electrical signals in muscles and nerves for physiological functions. Disorders in Nav channel activity have been shown to induce neurological pathologies and pain states. Here, we describe the current knowledge of CnTX isoform modulation of the Nav channel activity, the mechanism of action and the potential therapeutic use of these toxins in counteracting neurological dysfunctions.

Non-opioid therapeutics for the treatment of neuropathic pain are urgently needed to address the ongoing opioid crisis. Peptides from cone snail venoms have served as invaluable molecules to target key pain-related receptors but can suffer from unfavorable physicochemical properties, which limit their therapeutic potential. In this work, we developed conformationally constrained α-RgIA analogues with high potency, receptor selectivity, and enhanced human serum stability to target the human α9α10 nicotinic acetylcholine receptor. The key lactam linkage introduced in α-RgIA fixed the favored globular conformation and suppressed disulfide scrambling. The NMR structure of the macrocyclic peptide overlays well with that of α-RgIA4, demonstrating that the cyclization does not perturb the overall conformation of backbone and key side-chain residues. Finally, a molecular docking model was used to rationalize the selective binding between a macrocyclic analogue and the α9α10 nicotinic acetylcholine receptor. These conformationally constrained antagonists are therefore promising candidates for antinociceptive therapeutic intervention.

Lipomyelomeningocele (LMM) is a congenital spinal cord anomaly. While patients with LMM may initially be asymptomatic, neurological sequelae secondary to LMM may become apparent as the patient ages. Consequently, some pediatric neurosurgeons have advocated for upfront neurosurgical interventions irrespective of the presence of symptoms at diagnosis. By contrast, others pursue a conservative approach when overt neurological symptoms are not yet evident. In light of the various practice styles to the heterogeneous anatomical locations, symptoms, and ages associated with LMM, we have conducted a multi-center survey of Canadian pediatric neurosurgeons using clinical vignettes representative of LMM patients. An online survey of the opinions of Canadian pediatric neurosurgeons was conducted using 5 separate cases with magnetic resonance imaging (MRI) scans of the lumbar spine. Each case was accompanied with the same three clinical vignettes, which varied in severity at time of presentation: asymptomatic, progressive somatic motor deficit, or longstanding overflow incontinence. Participants were asked the question, “Would you offer surgical management?” after each clinical vignette. After the five cases and their corresponding 3 clinical vignettes, participants were asked, “If you answered yes to any of the preceding questions, what type of surgery would you perform?”. Options for surgical goals and techniques included complete removal, near-total removal, debulking, detethering, and expansile duroplasty. Surgical adjuncts included CUSA, LASER, and neurophysiologic monitoring. Twenty-three responses were received from the 38 questionnaires sent out to all staff pediatric neurosurgeons across academic medical centers in Canada. This represented a response rate of 61%. Canadian pediatric neurosurgeons generally maintain a conservative approach to the surgical management of LMM as only 13% (n = 3) of surgeons indicated that they would operate in all scenarios. By contrast, 43% (n = 10) indicated surgical management in only those cases presenting with symptoms, and another 43% (n = 10) displayed a variable surgical approach. Nine percent (n = 2) of participants would not perform surgery for incontinence. The greatest level of disagreement among participants pertained to the management of asymptomatic sacral LMM where 43% of participants favored prophylactic surgery, while 57% of participants preferred conservative management. The current study highlights the differences in management of LMM among Canadian pediatric neurosurgeons and provides further support for future prospective cohort studies to develop appropriate expert opinions and guidelines such that the care of LMM patients may be according to evidence-based best practice. This is especially true for the treatment of asymptomatic patients, a patient group that would benefit from a randomized controlled trial to assess the long-term outcomes of conservative and surgical management.

Predatory gastropods of the superfamily Conoidea number over 12,000 living species. The evolutionary success of this lineage can be explained by the ability of conoideans to produce complex venoms for hunting, defense, and competitive interactions. Whereas venoms of cone snails (family Conidae) have become increasingly well studied, the venoms of most other conoidean lineages remain largely uncharacterized. In the present study, we present the venom gland transcriptomes of two species of the genus Clavus that belong to the family Drilliidae. Venom gland transcriptomes of two specimens of Clavus canalicularis and two specimens of Clavus davidgilmouri were analyzed, leading to the identification of a total of 1,176 putative venom peptide toxins (drillipeptides). Based on the combined evidence of secretion signal sequence identity, entire precursor similarity search (BLAST), and the orthology inference, putative Clavus toxins were assigned to 158 different gene families. The majority of identified transcripts comprise signal, pro-, mature peptide, and post-regions, with a typically short (

The defensive use of cone snail venom is hypothesised to have first arisen in ancestral worm-hunting snails and later repurposed in a compartmentalised venom duct to facilitate the dietary shift to molluscivory and piscivory. Consistent with its placement in a basal lineage, we demonstrate that the

Cone snail venom biodiversity reflects dietary preference and predatory and defensive envenomation strategies across the ≈900 species of

α6β4 nAChR is expressed in the peripheral and central nervous systems and is associated with pain, addiction, and movement disorders. Natural α-conotoxins (α-CTxs) can effectively block different nAChR subtypes with higher efficacy and selectivity. However, the research on α6β4 nAChR is relatively poor, partly because of the lack of available target-specific α-CTxs. In this study, we synthesized a novel α-4/7 conotoxin QuIA that was found from Conus quercinus. We investigated the efficacy of this peptide to different nAChR subtypes using a two-electrode voltage-clamp technique. Remarkably, we found α-QuIA inhibited the neuronal α3β2 and α6/α3β4 nAChR subtypes with significantly high affinity (IC50 was 55.7 nM and 90.68 nM, respectively), and did not block other nAChR subtypes even at a high concentration of 10 μM. In contrast, most α-CTxs have been determined so far to effectively block the α6/α3β4 nAChR subtype while also maintaining a similar higher efficacy against the closely related α6β2β3 and/or α3β4 subtypes, which are different from QuIA. In conclusion, α-QuIA is a novel α4/7-CTx, which has the potential to develop as an effective neuropharmacology tool to detect the function of α6β4 nAChR.

The venom duct transcriptomes and proteomes of the cryptic cone snail species

α-Conotoxins GI and MI belong to the 3/5 subfamily of α-conotoxins and potently inhibit muscular nicotinic acetylcholine receptors (nAChRs). To date, no 3/4- or 3/6-subfamily α-conotoxins have been reported to inhibit muscular nAChRs. In the present study, a series of new 3/4-, 3/6-, and 3/7-subfamily GI and MI variants were synthesized and functionally characterized by modifications of loop2. The results show that the 3/4-subfamily GI variant GI[∆8G]-II and the 3/6-subfamily variants GI[+13A], GI[+13R], and GI[+13K] displayed potent inhibition of muscular nAChRs expressed in Xenopus oocytes, with an IC50 of 45.4–73.4 nM, similar to or slightly lower than that of wild-type GI (42.0 nM). The toxicity of these GI variants in mice appeared to be about a half to a quarter of that of wild-type GI. At the same time, the 3/7-subfamily GI variants showed significantly lower in vitro potency and toxicity. On the other hand, similar to the 3/6-subfamily GI variants, the 3/6-subfamily MI variants MI[+14R] and MI[+14K] were also active after the addition of a basic amino acid, Arg or Lys, in loop2, but the activity was not maintained for the 3/4-subfamily MI variant MI[∆9G]. Interestingly, the disulfide bond connectivity “C1–C4, C2–C3” in the 3/4-subfamily variant GI[∆8G]-II was significantly more potent than the “C1–C3, C2–C4” connectivity found in wild-type GI and MI, suggesting that disulfide bond connectivity is easily affected in the rigid 3/4-subfamily α-conotoxins and that the disulfide bonds significantly impact the variants’ function. This work is the first to demonstrate that 3/4- and 3/6-subfamily α-conotoxins potently inhibit muscular nAChRs, expanding our knowledge of α-conotoxins and providing new motifs for their further modifications.

Conotoxins are tools used by marine

Within the Conidae family, the piscivorous

In our work of screening analgesic peptides from the conotoxin libraries of diverse Conus species, we decoded a peptide sequence from Conus lividus and named it Lv32.1 (LvXXXIIA). The folding conditions of linear Lv32.1 on buffer, oxidizing agent, concentration of GSH/GSSG and reaction time were optimized for a maximum yield of (34.94 ± 0.96)%, providing an efficient solution for the synthesis of Lv32.1. Its disulfide connectivity was identified to be 1–3, 2–6, 4–5, which was first reported for the conotoxins with cysteine framework XXXII and different from the common connectivities established for conotoxins with six cysteines. The analgesic effect of Lv32.1 was determined by a hot plate test in mice. An evident increase in the pain threshold with time illustrated that Lv32.1 exhibited analgesic potency. The effects on Nav1.8 channel and α9α10 nAChR were detected, but weak inhibition was observed. In this work, we highlight the efficient synthesis, novel disulfide linkage and analgesic potential of Lv32.1, which laid a positive foundation for further development of conotoxin Lv32.1 as an analgesic candidate.