Avaliação das atividades funcionais da Bhalternina, identificação e síntese da região peptídica inibidora da agregação plaquetária

Abstract

Platelets plays important roles in primary hemostasis, which is responsible for hemostatic plug formation in the presence of vascular injury. The processes exerted by platelets consist of platelet adhesion, activation and aggregation, and imbalances in these mechanisms cause vascular occlusion, with consequent occurrence of thrombotic disease. This is considered a serious public health problem due to its high incidence and high mortality rate, and the available treatments have several limitations, such as increased risk of bleeding and unresponsiveness by patients. The search for new components that act on platelet function is extremely important for the diagnosis and treatment of these diseases, and snake venoms present substances capable of interfering with platelet function. There are several classes of ophidic proteins that interact with platelet receptors, and the peptides present in venom have stood out due to their lower complexity and lower production cost. The aim of this study was to evaluate the interference of bhalternin, a serinoprotease isolated from Bothrops alternatus venom, on platelet aggregation. As a result, it was found that the protein, after denatured, was able to inhibit platelet aggregation by interacting with the P2Y12 ADP receptor. In addition, the peptide region responsible for this activity has been identified and designated BhaltPIP, which has been synthesized and is in patenting process. The effect of bhalternin on tumor cells was also evaluated, and was noted that the protein interferes with prostate tumor cell growth without acting on the growth of normal cell. Thus, it is concluded that bhalternin has functions on both tumor cells and platelet aggregation, and the BhaltPIP peptide derived from this protein has therapeutic potential for treatment and diagnosis of hemostatic disorders.