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1.
J. venom. anim. toxins incl. trop. dis ; 28: e20210116, 2022. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1375812

RESUMO

Background: Conopeptides from cone snail venom have aroused great interest related to the discovery of novel bioactive candidates, due to their excellent prospects for the treatment of various health problems such as pain, addiction, psychosis and epilepsy. In order to explore novel biopeptides, we investigated the structure and function of five novel conopeptides isolated from the venom of Conus marmoreus from South China Sea. Methods: C. marmoreus crude venom was prepared, fractionated and purified by HPLC system. The primary sequences of the five novel disulfide-poor conopeptides Mr-1 to Mr-5 were identified by comprehensive analysis of de novo MALDI-TOF tandem mass spectrometry and Edman degradation data. In order to investigate their function, these five conopeptides were synthesized by Fmoc-SPPS chemistry, and their biological effects at several heterologous rat nicotinic acetylcholine receptor (nAChR) subtypes (α1β1δε, α3β2, α3β4, α4β2) were determined by electrophysiological technique. Results: Five novel disulfide-poor conopeptides were identified and named as follows: Mr-1 (DWEYHAHPKPNSFWT), Mr-2 (YPTRAYPSNKFG), Mr-3 (NVIQAPAQSVAPP NTST), Mr-4 [KENVLNKLKSK(L/I)] and Mr-5 [NAVAAAN(L/I)PG(L/I)V]. None of them contains a disulfide bond. The sequences of conopeptides Mr-2 to Mr-5 do not belong to any category of the known disulfide-poor conopeptides. No significant activity against the above nAChR subtypes were observed for the five conopeptides at 100 µM. Conclusion: We purified and structurally characterized five novel disulfide-poor conopeptides from C. marmoreus crude venom and first investigated their nAChR inhibitory effects. This work expanded our knowledge on the structure and function of disulfide-poor conopeptides from this cone snail venom.(AU)


Assuntos
Animais , Conotoxinas/isolamento & purificação , Dissulfetos/efeitos adversos , Venenos de Moluscos , Espectrometria de Massas
2.
J. venom. anim. toxins incl. trop. dis ; 27: e20210023, 2021. tab, graf, ilus, mapas
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1346437

RESUMO

Diverse and unique bioactive neurotoxins known as conopeptides or conotoxins are produced by venomous marine cone snails. Currently, these small and stable molecules are of great importance as research tools and platforms for discovering new drugs and therapeutics. Therefore, the characterization of Conus venom is of great significance, especially for poorly studied species. Methods: In this study, we used bioanalytical techniques to determine the venom profile and emphasize the functional composition of conopeptides in Conus taeniatus, a neglected worm-hunting cone snail. Results: The proteomic analysis revealed that 84.0% of the venom proteins were between 500 and 4,000 Da, and 16.0% were > 4,000 Da. In C. taeniatus venom, 234 peptide fragments were identified and classified as conotoxin precursors or non-conotoxin proteins. In this process, 153 conotoxin precursors were identified and matched to 23 conotoxin precursors and hormone superfamilies. Notably, the four conotoxin superfamilies T (22.87%), O1 (17.65%), M (13.1%) and O2 (9.8%) were the most abundant peptides in C. taeniatus venom, accounting for 63.40% of the total conotoxin diversity. On the other hand, 48 non-conotoxin proteins were identified in the venom of C. taeniatus. Moreover, several possibly biologically active peptide matches were identified, and putative applications of the peptides were assigned. Conclusion: Our study showed that the composition of the C. taeniatus-derived proteome is comparable to that of other Conus species and contains an effective mix of toxins, ionic channel inhibitors and antimicrobials. Additionally, it provides a guidepost for identifying novel conopeptides from the venom of C. taeniatus and discovering conopeptides of potential pharmaceutical importance.(AU)


Assuntos
Animais , Proteoma , Conotoxinas , Caramujo Conus , Venenos de Moluscos , Neurotoxinas , Produtos Biológicos
3.
J. venom. anim. toxins incl. trop. dis ; 27: e20200164, 2021. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1279407

RESUMO

Background Conotoxins have become a research hotspot in the neuropharmacology field for their high activity and specificity in targeting ion channels and neurotransmitter receptors. There have been reports of a conotoxin acting on two ion channels, but rare reports of a conotoxin acting on three ion channels. Methods Vr3a, a proline-rich M-superfamily conotoxin from a worm-hunting Conus varius, was obtained by solid-phase synthesis and identified by mass spectrometry. The effects of synthesized Vr3a on sodium, potassium and calcium currents were tested on rat DRG cells by patch clamp experiments. The further effects of Vr3a on human Cav1.2 and Cav2.2 currents were tested on HEK293 cells. Results About 10 μM Vr3a has no effects on the peak sodium currents, but can induce a ~10 mV shift in a polarizing direction in the current-voltage relationship. In addition, 10 μM Vr3a can increase 19.61 ± 5.12% of the peak potassium currents and do not induce a shift in the current-voltage relationship. An amount of 10 μM Vr3a can inhibit 31.26% ± 4.53% of the peak calcium currents and do not induce a shift in the current-voltage relationship. The IC50 value of Vr3a on calcium channel currents in rat DRG neurons is 19.28 ± 4.32 μM. Moreover, 10 μM Vr3a can inhibit 15.32% ± 5.41% of the human Cav1.2 currents and 12.86% ± 4.93% of the human Cav2.2 currents. Conclusions Vr3a can simultaneously affect sodium, potassium and calcium currents. This novel triple-target conotoxin Vr3a expands understanding of conotoxin functions.(AU)


Assuntos
Prolina/análise , Conotoxinas/análise , Potássio , Sódio , Cálcio
4.
J. venom. anim. toxins incl. trop. dis ; 26: e20190095, 2020. tab, graf, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1135162

RESUMO

Conopeptides are neuropharmacological peptides derived from the venomous salivary glands of cone snails. Among 29 superfamilies based on conserved signal sequences, T-superfamily conotoxins, which belong to the smallest group, include four different frameworks that contain four cysteines denominated I, V, X and XVI. In this work, the primary structure and the cysteine connectivity of novel conotoxin of Conus bandanus were determined by tandem mass spectrometry using collision-induced dissociation. Methods: The venom glands of C. bandanus snails were dissected, pooled, and extracted with 0.1% trifluoroacetic acid in three steps and lyophilized. The venom was fractionated and purified in an HPLC system with an analytical reversed-phase C18 column. The primary peptide structure was analyzed by MALDI TOF MS/MS using collision-induced dissociation and confirmed by Edman's degradation. The peptide's cysteine connectivity was determined by rapid partial reduction-alkylation technique. Results: The novel conotoxin, NGC1C2(I/L)VREC3C4, was firstly derived from de novo sequencing by MS/MS. The presence of isoleucine residues in this conotoxin was confirmed by the Edman degradation method. The conotoxin, denominated Bn5a, belongs to the T1-subfamily of conotoxins. However, the disulfide bonds (C1-C4/C2-C3) of Bn5a were not the same as found in other T1-subfamily conopeptides but shared common connectivities with T2-subfamily conotoxins. The T1-conotoxin of C. bandanus proved the complexity of the disulfide bond pattern of conopeptides. The homological analysis revealed that the novel conotoxin could serve as a valuable probe compound for the human-nervous-system norepinephrine transporter. Conclusion: We identified the first T1-conotoxin, denominated Bn5a, isolated from C. bandanus venom. However, Bn5a conotoxin exhibited unique C1-C4/C2-C3 disulfide connectivity, unlike other T1-conotoxins (C1-C3/C2-C4). The structural and homological analyses herein have evidenced novel conotoxin Bn5a that may require further investigation.(AU)


Assuntos
Animais , Peptídeos , Conotoxinas , Dissulfetos , Caramujo Conus , Glândulas Salivares
5.
J. venom. anim. toxins incl. trop. dis ; 22: 30, 2016. tab, graf, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-954780

RESUMO

During evolution, nature has embraced different strategies for species to survive. One strategy, applied by predators as diverse as snakes, scorpions, sea anemones and cone snails, is using venom to immobilize or kill a prey. This venom offers a unique and extensive source of chemical diversity as it is driven by the evolutionary pressure to improve prey capture and/or to protect their species. Cone snail venom is an example of the remarkable diversity in pharmacologically active small peptides that venoms can consist of. These venom peptides, called conopeptides, are classified into two main groups based on the number of cysteine residues, namely disulfide-rich and disulfide-poor conopeptides. Since disulfide-poor conotoxins are minor components of this venom cocktail, the number of identified peptides and the characterization of these peptides is far outclassed by its cysteine-rich equivalents. This review provides an overview of 12 families of disulfide-poor peptides identified to date as well as the state of affairs.(AU)


Assuntos
Peptídeos , Caramujos , Conotoxinas , Venenos de Moluscos
6.
J. venom. anim. toxins incl. trop. dis ; 20: 1-6, 04/02/2014. tab, graf, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1484561

RESUMO

Calcium channel blockers such as conotoxins have shown a great potential to reduce brain and spinal cord injury. MVIIC neuroprotective effects analyzed in in vitro models of brain and spinal cord ischemia suggest a potential role of this toxin in preventing injury after spinal cord trauma. However, previous clinical studies with MVIIC demonstrated that clinical side effects might limit the usefulness of this drug and there is no research on its systemic effects. Therefore, the present study aimed to investigate the potential toxic effects of MVIIC on organs and to evaluate clinical and blood profiles of rats submitted to spinal cord injury and treated with this marine toxin. Rats were treated with placebo or MVIIC (at doses of 15, 30, 60 or 120 pmol) intralesionally following spinal cord injury. Seven days after the toxin administration, kidney, brain, lung, heart, liver, adrenal, muscles, pancreas, spleen, stomach, and intestine were histopathologically investigated. In addition, blood samples collected from the rats were tested for any hematologic or biochemical changes.


Assuntos
Animais , Ratos , Bloqueadores dos Canais de Cálcio/análise , Conotoxinas/análise , Cérebro/anatomia & histologia , Ferimentos e Lesões , Medula Óssea , Ratos
7.
Artigo em Inglês | LILACS | ID: lil-724671

RESUMO

Calcium channel blockers such as conotoxins have shown a great potential to reduce brain and spinal cord injury. MVIIC neuroprotective effects analyzed in in vitro models of brain and spinal cord ischemia suggest a potential role of this toxin in preventing injury after spinal cord trauma. However, previous clinical studies with MVIIC demonstrated that clinical side effects might limit the usefulness of this drug and there is no research on its systemic effects. Therefore, the present study aimed to investigate the potential toxic effects of MVIIC on organs and to evaluate clinical and blood profiles of rats submitted to spinal cord injury and treated with this marine toxin. Rats were treated with placebo or MVIIC (at doses of 15, 30, 60 or 120 pmol) intralesionally following spinal cord injury. Seven days after the toxin administration, kidney, brain, lung, heart, liver, adrenal, muscles, pancreas, spleen, stomach, and intestine were histopathologically investigated. In addition, blood samples collected from the rats were tested for any hematologic or biochemical changes.


Assuntos
Animais , Ratos , Medula Óssea , Bloqueadores dos Canais de Cálcio/análise , Cérebro/anatomia & histologia , Conotoxinas/análise , Ferimentos e Lesões , Ratos
8.
Univ. med ; 54(1): 10-25, ene.-mar. 2013. ilus, graf
Artigo em Espanhol | LILACS | ID: lil-703243

RESUMO

Introducción: El diseño de instrumentos o moléculas inspiradas en la naturaleza hapermitido avanzar en diferentes áreas de la ciencia y tecnología. Objetivo: Evaluarcambios plásticos a corto plazo desencadenados por la administración intraperitonealde un péptido agonista del receptor de glutamato NMDA. Materiales y métodos:Se utilizaron ratas macho divididas en grupo péptido (a quienes se administróperitonealmente el péptido) y grupo control (a quienes se administró peritonealmenteel vehículo). Por técnicas de estereotaxia se localizaron electrodos de estimulacióny registro en las áreas hipocampales CA3 y CA1 respectivamente, con el ánimo deobtener los potenciales de campo y analizar cambios en su pendiente y amplitud porla aplicación de pares de estímulos, antes y después de la administración del péptido.Resultados: Aunque con la administración del péptido no hay cambios en variablessistémicas como la temperatura o la frecuencia cardiaca, sí se pueden modificar lospotenciales de campo, específicamente cuando el intervalo entre pares de estímuloses más corto (40 a 80 ms). Conclusión: El péptido evaluado en el presente trabajotiene efectos en la facilitación por pulsos pareados tanto en la amplitud como en lapendiente de potenciales de campo en el hipocampo de ratas, pero en los intervalosentre estímulos más cortos...


Introduction: Designing bio-inspired devicesor molecules has been a longstanding methodsupporting multiple advances in science and technology.Objective: To test the potential effectof intraperitoneal administration of the bio-inspiredpeptide on short-term plasticity. Materialsand methods: Male rats in two groups (peptidetreated and control) were used for registrationof hippocampal field potentials from CA1, afterpaired stimuli in CA3 contra lateral area. Results:Amplitude and slope of field potentials’,both before and after peptide administration,showed no changes in systemic factors (temperatureand heart rate), but statistical significancein short term plasticity in small inter stimuli interval(40 to 80 ms). Conclusion: The current researchshows effects on paired pulse facilitationcaused by peptide treatment, specifically on interstimuli interval shorter...


Assuntos
Conotoxinas , Hipocampo , Toxicologia
9.
Rev. Soc. Bras. Med. Trop ; 39(5): 498-500, set.-out. 2006. ilus
Artigo em Inglês | LILACS | ID: lil-439904

RESUMO

Mollusks of the genus Conus present a venomous apparatus composed of radulae, a chitin structure linked to glands, which injects potent neurotoxic peptides, causing serious human envenomation and even death, associated with the blockage of certain receptors and muscular paralysis. No reported envenomation has occurred in Brazil, but certain populations are at risk of accidents.


Os moluscos do gênero Conus apresentam um aparato venenoso composto de uma rádula quitinosa ligada a glândulas de peçonha, causando envenenamentos humanos graves e mesmo óbitos pela ação neurotóxica indutora do bloqueio de vários receptores e paralisia muscular. Não há casos descritos de envenenamento no país, mas determinadas populações correm risco de acidentes.


Assuntos
Humanos , Animais , Caramujo Conus , Conotoxinas/toxicidade , Venenos de Moluscos/toxicidade , Neurotoxinas/toxicidade , Brasil , Fatores de Risco
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