RESUMEN
Hypervalent tellurium compounds have a particular reactivity towards thiol compounds which are related to their biological properties. In this work, this property was assembled to tellurium-functionalized surfaces. These compounds were used as linkers in the immobilization process of thiolated biomolecules (such as DNA) on microcantilever surfaces. The telluride derivatives acted as reversible binding agents due to their redox properties, providing the regeneration of microcantilever surfaces and allowing their reuse for further biomolecules immobilizations, recycling the functional surface. Initially, we started from the synthesis of 4-((3-((4-methoxyphenyl) tellanyl) phenyl) amino)-4-oxobutanoic acid, a new compound, which was immobilized on a silicon surface. In nanomechanical systems, the detection involved a hybridization study of thiolated DNA sequences. Fluorescence microscopy technique was used to confirm the immobilization and removal of the telluride-DNA system and provided revealing results about the potentiality of applying redox properties to chalcogen derivatives at surfaces.
Asunto(s)
Técnicas Biosensibles , ADN/química , Silicio/química , Telurio/química , Secuencia de Bases/genética , Nanoestructuras/química , Hibridación de Ácido Nucleico , Compuestos de Sulfhidrilo/química , Propiedades de SuperficieRESUMEN
In this work, we aim to provide evidence for the protective effect of a copper chelator, neocuproine (NeoCu), against the oxidative stress in NSC34 cells, which inhibits biomolecule oxidation and cell death. Results obtained with the comet assay allowed to determine the increase in oxidized purines and pyrimidines by H2O2 exposure, and their changes after the addition of NeoCu. We also observed a higher ATP7b activity in nuclei and a higher Cu concentration inside the cells, proving that the NeoCu acts directly in DNA to promote cell recovery in oxidative stress conditions, also observed in Reactive Oxygen Species (ROS) detection assay by Flow Cytometry. Based on these results, we propose that NeoCu is a promising drug for the protection of motor neuron cells during oxidative stress caused by neurodegenerative diseases in this system.
Asunto(s)
Quelantes/farmacología , Daño del ADN , Peróxido de Hidrógeno/toxicidad , Neuroblastoma/prevención & control , Estrés Oxidativo/efectos de los fármacos , Fenantrolinas/farmacología , Sustancias Protectoras/farmacología , Cobre/metabolismo , ATPasas Transportadoras de Cobre/metabolismo , Humanos , Neuroblastoma/patología , Oxidantes/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Células Tumorales CultivadasRESUMEN
About 1 in 8 U.S. women (≈12%) will develop invasive breast cancer over the course of their lifetime. Surgery, chemotherapy, radiotherapy, and hormone manipulation constitute the major treatment options for breast cancer. Here, we show that both a natural antimicrobial peptide (AMP) derived from wasp venom (decoralin, Dec-NH2), and its synthetic variants generated via peptide design, display potent activity against cancer cells. We tested the derivatives at increasing doses and observed anticancer activity at concentrations as low as 12.5 µmol L-1 for the selective targeting of MCF-7 breast cancer cells. Flow cytometry assays further revealed that treatment with wild-type (WT) peptide Dec-NH2 led to necrosis of MCF-7 cells. Additional atomic force microscopy (AFM) measurements indicated that the roughness of cancer cell membranes increased significantly when treated with lead peptides compared to controls. Biophysical features such as helicity, hydrophobicity, and net positive charge were identified to play an important role in the anticancer activity of the peptides. Indeed, abrupt changes in peptide hydrophobicity and conformational propensity led to peptide inactivation, whereas increasing the net positive charge of peptides enhanced their activity. We present peptide templates with selective activity towards breast cancer cells that leave normal cells unaffected. These templates represent excellent scaffolds for the design of selective anticancer peptide therapeutics.