Ciclótidos, proteínas circulares producidas por plantas con potencial farmacológico / Cyclotides, circular proteins produced by plants with pharmacological potential

Los ciclótidos son proteínas circulares de alrededor de 28 a 37 residuos de aminoácidos, poseen una marcada importancia biológica gracias a su estructura cíclica que le proporciona estabilidad. En este estudio se realizó una búsqueda bibliográfica en las bases de datos EBSCOHOST, Science Direct, Pubmed y ACS publication. Los artículos seleccionados entre los años 2010 a 2014 contenían las palabras claves cyclotides, cyclic peptides, macrocyclic peptides y drugs, se seleccionaron teniendo en cuenta como criterios de inclusión artículos con texto completo en ingles, de investigaciones experimentales originales, relacionadas con el uso de ciclótidos para el diseño de fármacos. Mediante el análisis de los artículos se encontró que los ciclótidos tienen un amplio rango de bioactividades tales como insecticida, uterotónica, antimicrobiana, antiVIH, anticáncer, hemolítica, antagonista de la neurotensina e inhibidora de la tripsina por lo cual se pueden emplear como bases para la elaboración de nuevos fármacos que puedan ser aplicados al tratamiento de distintas enfermedades(AU)

The ciclotydes are circular proteins of 28 to 37 aminoacid that have a unique and strong cyclic structural motif which confers stability and relevant biological activities. In this study we searched in data bases EBSCOHOST, Science Direct, Pubmed and ACS publication to identify relevant studies considering inclusion criteria such as full-text articles in English, original experimental research related to the use of cyclotides in drug design. The biological activities of the cyclotides have been reported as insecticide, uterotonic, antimicrobial, antiHIV, anticancer, hemolytic, neurotensin antagonist and inhibitor of trypsin which can be used as basis for the development of new drugs that can be applied to the treatment of various diseases(AU)

A cyclotide against influenza A H1N1 virus from Viola yedoensis / 药学学报

Three cyclotides were isolated from the whole plant of Viola yedoensis in this study. The two, vary peptide E and cycloviolacin Y5, were previously reported, and a novel cycloviolacin VY1 was characterized according to the interpretation of MS/MS fragmentation of peptides which were produced from the reduced and alkylated parent peptide with the digestion of Endo Lys-C, trypsin and chymotrypsin, separately. The stability of remarkable resistance to proteolytic degradation by trypsin and chymotrypsin, and that of thermal denaturation was confirmed again. Besides, the IC50 value of cycloviolacin VY1 against influenza A H1N1 virus was (2.27 +/- 0.20) microg x mL(-1). It is the first cyclotide reported with anti-influenza A H1N1 virus activity in vitro assay.

Elucidating the structure of two cyclotides of Viola tianshanica maxim by MALDI TOF/TOF MS analysis / 药学学报

The cyclotides are a family of cyclic "mini" proteins that occur in Violaceae, Rubiaceae and Cucurbitaceae plant families and contain a head-to-tail cyclic backbone and a cystine knot arranged by three disulfide bonds. To study the natural cyclotides of V tianshanica, dried herb was extracted with 50% ethanol, and the concentrated aqueous extract was subjected to a solvent-solvent partitioning between water and hexane, ethyl acetate and n-butanol, separately. The n-butanol extract containing cyclotides was subjected to column chromatography over Sephadex LH-20, eluted with 30% methanol. The subfractions were directly reduced by DTT and analyzed by reverse-phase HPLC. The peaks with different retention times were shown on the profile of RP-HPLC and collected. The cyclotides were speculated based on masses range from 3 000 to 3 500 Da. The purified cyclotides were reduced with DTT, alkylated with iodoacetamide, and then were cleaved with endoproteinase Glu-C, endoproteinase Lys-C and Trypsin, separately. The digested peptides were purified on RP-HPLC and analyzed on MALDI TOF/TOF analyzer. A new cyclotide, cycloviolacin T1 and a reported cyclotide varv E were systemically determined using MALDI TOF/TOF system. So the method for the isolation and characterization of cyclotides was quickly built up in succession.