Análise da interação de 2-N-alquilpiridilporfirinas catiônicas com proteínas envolvidas na dinâmica de Ca2+ em cardiomiócitos

• Ano de defesa: 2022
• Autor(a) principal: Barreto, Nícolas Albuquerque
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal da Paraíba; Brasil; Biotecnologia; Programa de Pós-Graduação em Biotecnologia; UFPB
• Palavras-chave em Português: Doenças cardiovasculares; Canal de cálcio (Cav1.2).; Cardiomiócitos; Docking molecular; Porfirinas; Troponina C.; Cardiovascular diseases; Calcium channel (Cav1.2).; Cardiomyocytes; Molecular docking; Porphyrins; Troponin C.; CNPQ::CIENCIAS BIOLOGICAS
• Link de acesso: https://repositorio.ufpb.br/jspui/handle/123456789/29830

Cardiovascular diseases (CVDs) are the leading cause of the death across the globe with myocardial infarction being responsible for 17.9 million of death in 2017. Factors such as sedentarism, unhealthy diet, alcoholism, changes in Ca2+ homeostasis and redox homeostasis are already well described as CVDS triggers. Among molecules with potential redox modulation capability and therapeutic potential are porphyrins and metaloporphyrins. Our research group and collaborators in 2020 described MnTE-2- PyP5+ as capable of modulating Ca2+ in vivo and in vitro, but this activity was not assigned to its redox modulation capability. Thus, the main goal of this work was to analyze trough molecular docking how porphyrins interact with proteins involved in the excitation-contraction coupling. CaVAb a Calcium channel with bacterial origin and a complex of cardiac troponin C with a fragment from cardiac troponin I were used. It was observed that the two used porphyrins meso-tetrakis (N-methylpiridin-2- yl)porphyrin and meso-tetrakis(N-ethylpiridin-2-yl)porphyrin obtained good affinity values for CaVAb, both in blind docking protocol and in known active site binding. As for troponin C, it was observed a major interaction with the N domain of the protein, different from the known binding site for this structure. Therefore, it was possible to conclude that the used porphyrins, based on the values of affinity found have a high potential to modulate CaVAb and low potential do sensibilize the troponin C to Ca2+