Atualmente, diferentes classes funcionais de peptídeos e toxinas biologicamente ativas isolados de diversos organismos são conhecidas. Em medicina, esses polipeptídios podem ser diretamente utilizados ou podem servir como modelos para a geração de moléculas derivadas. Aqui, nós fazemos referência a três classes de peptídeos e toxinas que agem sobre membranas celulares ou sobre sistemas de transporte por membranas: (i) toxinas binárias; (ii) peptídeos antimicrobianos; (iii) peptídeos penetradores de células. As toxinas binárias têm sido geneticamente manipuladas para gerar imunotoxinas específicas, enquanto os peptídeos antimicrobianos são usados como agentes alternativos contra células tumorais e microbianas resistentes. Os peptídeos penetradores de células têm aplicações que vão desde a transfecção celular quanto ao transporte intracelular de nanopartículas. Nosso grupo vem investigando a capacidade da crotamina, um peptídeo do veneno de cascavel, em translocar membranas celulares, bem como de utilizar a crotamina como sistema de transporte molecular e de análise de imagens.Today, different functional classes of bioactive peptides and toxins isolated from diverse sources of living organisms are known. In medicine, these polypeptides present the potential to be used structurally unmodified or to serve as templates for molecular design of improved derivatives. Here, we refer to members of three classes of remarkable peptides and toxins that act at the cell membranes level and membrane trafficking systems: (i) the binary toxins (ii) the antimicrobial peptides and (iii) the cell penetrating peptides. Binary toxins have been genetically manipulated to generate specific immunotoxins, while antimicrobial peptides are in use as alternative agents against resistant microbes and tumor cells. Cell penetrating peptides have applications as diverse as cell transfection and transport of nanomaterials. Our group is dissecting the capacity of crotamine, a peptide from rattlesnake venom, to translocate cell membranes and use it as a delivery system in the transducing technology and molecular imaging.Keywords: cytolysin, binary toxin, antimicrobial peptide, cell-penetrating peptide, animal toxin, nanobiotechnology Binary Bacterial ToxinsA wide variety of bacterial toxins that has the cell membrane as a target is presently known. Indeed the molecular diversity of bacterial toxins is so remarkable that a large number of microorganisms secret several toxic peptides and polypeptides devoid of or having catalytic activity. All these toxins are capable of intoxicating eucaryotic cells by interfering directly with cytoplasmic membrane or by using membrane systems to gain access Membrane-translocating Peptides and Toxins: from Nature to Bedside J. Braz. Chem. Soc. 212 to the interior of cells for the delivery of their active domain.In the first case, single chain proteins or composed of two separate water-soluble proteins -which oligomerize during their action on phospholipid membrane and form pores or channels -encompass the cytoly...
This work describes for the first time the characterization of the enzymatic features of gyroxin, a serine protease from Crotalus durissus terrificus venom, capable to induce barrel rotation syndrome in rodents. Measuring the hydrolysis of the substrate ZFR-MCA, the optimal pH for proteolytic cleavage of gyroxin was found to be at pH 8.4. Increases in the hydrolytic activity were observed at temperatures from 25 °C to 45 °C, and increases of NaCl concentration up to 1 M led to activity decreases. The preference of gyroxin for Arg residues at the substrate P1 position was also demonstrated. Taken together, this work describes the characterization of substrate specificity of gyroxin, as well as the effects of salt and pH on its enzymatic activity.
Background: This work aims to present a nuclear medicine imaging service's data regarding applying positron emission–computing tomography (PET/CT) scans with the radiopharmaceutical 68Ga-PSMA-HBED-CC (68Ga-PSMA-11) to diagnose prostate cancer clinical relapse. Methods: Eighty patients with a mean age of 68.26 years with an average prostatic-specific antigen blood level of 7.49 ng/ml (lower concentration = 0.17 ng/ml) received 68Ga-PSMA-11 intravenously, and full-body images of PT-CT scanning were obtained. Of the total of patients admitted to the imaging service, 87.5% were examined for disease's biochemical recurrence and clinical relapse, and 70.0% had a previous radical prostatectomy (RP). Results: Of the patients without RP, 95.8% had detection of intra-glandular disease. The 68Ga-PSMA-11 PET/CT imaging results revealed small lesions, even in patients with low blood levels of prostatic-specific antigen, mainly in metastatic cancer cases in lymph nodes and bones. Conclusion: The 68Ga-PSMA-11 PET/CT imaging was essential in detecting prostate cancer, with significantly high sensitivity in detecting recurrent cases. Due to its inherent reliability and sensitivity, PET/CT scanning with 68Ga-PSMA-11 received an increasing number of medical requests throughout the present follow-up study, confirming the augmented demand for this clinical imaging procedure in the regional medical community.
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