Toxic Peptides from the Mexican Scorpion : Chemical Structure and Evaluation of Recognition by Human Single-Chain Antibodies

Overview

Journal Toxins (Basel)

Publisher MDPI

Specialty Toxicology

Date 2024 Jul 26

PMID 39057941

Authors

Lidia Riano-Umbarila

Timoteo Olamendi-Portugal

Jose Alberto Romero-Moreno

Gustavo Delgado-Prudencio

Fernando Z Zamudio

Baltazar Becerril

Lourival D Possani

Affiliations

Soon will be listed here.

Abstract

Alternative recombinant sources of antivenoms have been successfully generated. The application of such strategies requires the characterization of the venoms for the development of specific neutralizing molecules against the toxic components. Five toxic peptides to mammals from the Mexican scorpion were isolated by chromatographic procedures by means of gel filtration on Sephadex G-50, followed by ion-exchange columns on carboxy-methyl-cellulose (CMC) resins and finally purified by high-performance chromatography (HPLC) columns. Their primary structures were determined by Edman degradation. They contain 66 amino acids and are maintained well packed by four disulfide bridges, with molecular mass from 7511.3 to 7750.1 Da. They are all relatively toxic and deadly to mice and show high sequence identity with known peptides that are specific modifiers of the gating mechanisms of Na ion channels of type beta-toxin (β-ScTx). They were named Cv1 to Cv5 and used to test their recognition by single-chain variable fragments (scFv) of antibodies, using surface plasmon resonance. Three different scFvs generated in our laboratory (10FG2, HV, LR) were tested for recognizing the various new peptides described here, paving the way for the development of a novel type of scorpion antivenom.

References

Gomez-Ramirez I, Riano-Umbarila L, Olamendi-Portugal T, Restano-Cassulini R, Possani L, Becerril B . Biochemical, electrophysiological and immunological characterization of the venom from Centruroides baergi, a new scorpion species of medical importance in Mexico. Toxicon. 2020; 184:10-18. DOI: 10.1016/j.toxicon.2020.05.021. View

Noble J, Bailey M . Quantitation of protein. Methods Enzymol. 2009; 463:73-95. DOI: 10.1016/S0076-6879(09)63008-1. View

Katoh K, Standley D . MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol. 2013; 30(4):772-80. PMC: 3603318. DOI: 10.1093/molbev/mst010. View

Xia Z, He D, Wu Y, Kwok H, Cao Z . Scorpion venom peptides: Molecular diversity, structural characteristics, and therapeutic use from channelopathies to viral infections and cancers. Pharmacol Res. 2023; 197:106978. DOI: 10.1016/j.phrs.2023.106978. View

MEVES H, Rubly N, WATT D . Effect of toxins isolated from the venom of the scorpion Centruroides sculpturatus on the Na currents of the node of Ranvier. Pflugers Arch. 1982; 393(1):56-62. DOI: 10.1007/BF00582392. View

Sorensen C, Ledsgaard L, Wildenauer H, Dahl C, Ebersole T, Bohn M . Cross-reactivity trends when selecting scFv antibodies against snake toxins using a phage display-based cross-panning strategy. Sci Rep. 2023; 13(1):10181. PMC: 10287648. DOI: 10.1038/s41598-023-37056-6. View

Restano-Cassulini R, Olamendi-Portugal T, Riano-Umbarila L, Zamudio F, Delgado-Prudencio G, Becerril B . Characterization of Sodium Channel Peptides Obtained from the Venom of the Scorpion . Toxins (Basel). 2024; 16(3). PMC: 10974992. DOI: 10.3390/toxins16030125. View

Riano-Umbarila L, Ledezma-Candanoza L, Serrano-Posada H, Fernandez-Taboada G, Olamendi-Portugal T, Rojas-Trejo S . Optimal Neutralization of Centruroides noxius Venom Is Understood through a Structural Complex between Two Antibody Fragments and the Cn2 Toxin. J Biol Chem. 2015; 291(4):1619-1630. PMC: 4722445. DOI: 10.1074/jbc.M115.685297. View

BABIN D, WATT D, Goos S, Mlejnek R . Amino acid sequence of neurotoxin I from Centruroides sculpturatus Ewing. Arch Biochem Biophys. 1975; 166(1):125-34. DOI: 10.1016/0003-9861(75)90371-9. View

10.

Cestele S, Yarov-Yarovoy V, Qu Y, Sampieri F, Scheuer T, Catterall W . Structure and function of the voltage sensor of sodium channels probed by a beta-scorpion toxin. J Biol Chem. 2006; 281(30):21332-21344. PMC: 1551974. DOI: 10.1074/jbc.M603814200. View

11.

Ortiz E, Gurrola G, Schwartz E, Possani L . Scorpion venom components as potential candidates for drug development. Toxicon. 2014; 93:125-35. PMC: 7130864. DOI: 10.1016/j.toxicon.2014.11.233. View

12.

Stothard P . The sequence manipulation suite: JavaScript programs for analyzing and formatting protein and DNA sequences. Biotechniques. 2000; 28(6):1102, 1104. DOI: 10.2144/00286ir01. View

13.

Gonzalez-Santillan E, Possani L . North American scorpion species of public health importance with a reappraisal of historical epidemiology. Acta Trop. 2018; 187:264-274. DOI: 10.1016/j.actatropica.2018.08.002. View

14.

Garcia-Guerrero I, Carcamo-Noriega E, Gomez-Lagunas F, Gonzalez-Santillan E, Zamudio F, Gurrola G . Biochemical characterization of the venom from the Mexican scorpion Centruroides ornatus, a dangerous species to humans. Toxicon. 2019; 173:27-38. DOI: 10.1016/j.toxicon.2019.11.004. View

15.

Riano-Umbarila L, Rodriguez-Rodriguez E, Santibanez-Lopez C, Guereca L, Uribe-Romero S, Gomez-Ramirez I . Updating knowledge on new medically important scorpion species in Mexico. Toxicon. 2017; 138:130-137. DOI: 10.1016/j.toxicon.2017.08.022. View

16.

Gurevitz M . Mapping of scorpion toxin receptor sites at voltage-gated sodium channels. Toxicon. 2012; 60(4):502-11. DOI: 10.1016/j.toxicon.2012.03.022. View

17.

Chippaux J . Emerging options for the management of scorpion stings. Drug Des Devel Ther. 2012; 6:165-73. PMC: 3401053. DOI: 10.2147/DDDT.S24754. View

18.

Jean-Philippe C, Alfredo C, Leslie B, Alejandro A . Factors involved in the resilience of incidence and decrease of mortality from scorpion stings in Mexico. Toxicon. 2020; 188:65-75. DOI: 10.1016/j.toxicon.2020.10.011. View

19.

Riano-Umbarila L, Gomez-Ramirez I, Ledezma-Candanoza L, Olamendi-Portugal T, Rodriguez-Rodriguez E, Fernandez-Taboada G . Generation of a Broadly Cross-Neutralizing Antibody Fragment against Several Mexican Scorpion Venoms. Toxins (Basel). 2019; 11(1). PMC: 6356842. DOI: 10.3390/toxins11010032. View

20.

Catterall W, Goldin A, Waxman S . International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol Rev. 2005; 57(4):397-409. DOI: 10.1124/pr.57.4.4. View