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This work was partially funded by the National Council of Scientific Research and Development (CNPq), the Ministry of Science, Technology and Innovation (MCTI), the Federal Government of Brazil, grants # 200,570/2022-6 and 305,316/2021-4, and the State of Ceara Foundation for Scientific and Technological Development (FUNCAP), State Government of Ceara, Brazil (grant # PR2-0101-00059.01.00/15). A.T.S is a fellowship recipient from the interuniversity exchange doctorate program (CNPq, grant #200570/2022-6).

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The anti-infective crotalicidin peptide analog RhoB-Ctn[1-9] is harmless to bovine oocytes and able to induce parthenogenesis in vitro

Publicated to:TOXICON. 234 107274-107274 - 2023-10-01 234(), DOI: 10.1016/j.toxicon.2023.107274

Authors: dos Santos, Ariane Teixeira; Albuquerque, Joao Victor da Silva; Arcce, Irving Mitchell Laines; Chaves, Otavio Augusto; Cruz, Gabriela Silva; Carretero, Victoria Jimenez; Melo, Luciana Magalhaes; Chaves, Maiana Silva; Guijo, Jesus Miguel Hernandez; Freitas, Vicente Jose de Figueiredo; Radis-Baptista, Gandhi

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Abstract

Crotalicidin is a cathelicidin-related anti-infective (antimicrobial) peptide expressed in the venom glands of the South American rattlesnake Crotalus durissus terrificus. Congener peptides of crotalicidin, named vipericidins, are found in other pit vipers inhabiting South America. Crotalicidin is active against bacteria and pathogenic yeasts and has anti-proliferative activity for some cancer cells. The structural dissection of crotalicidin produced fragments (e.g., Ctn [15-34]) with multiple biological functionalities that mimic the native peptide. Another structural characteristic of crotalidicin and congeners is a unique repetitive stretch of amino acid sequences in tandem embedded in their primary structures. One of the encrypted vipericidn peptides (Ctn [1-9]) was synthesized, and the analog covalently conjugated with rhodamine B (RhoB-Ctn [1-9]) displayed considerable antimicrobial activity and selective cytotoxicity. Methods to evaluate antimicrobial peptides' toxicity include lysis of red blood cells (hemolysis) in vitro and cytotoxicity of healthy cultured cells (e.g., fibroblasts). Here, as a non-conventional model of toxicity, the bovine oocytes were exposed to two standardized concentrations of RhoB-Ctn [1-9], and embryo viability and development at its first stage of cleavage (division of cells) and blastocyst formation were evaluated. Oocytes treated with peptide at 10 and 40 μM induced cleavage rates of 44.94% and 51.53%, resulting in the formation of blastocysts of 7.07% and 11.73%, respectively. Light sheet microscopy and in silico prediction analysis indicated that RhoB-Ctn [1-9] peptide interacts with zona pellucida and internalizes into bovine oocytes and developing embryos. The ADMET prediction estimated good bioavailability of RhoB-Ctn [1-9]. In conclusion, the peptide appeared harmless to bovine oocytes and, remarkably, activated the parthenogenesis in vitro at some level.Copyright © 2023. Published by Elsevier Ltd.

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