Publication: Cristalografía aplicada a la lucha frente al cáncer
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2016
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Abstract
El cáncer es una de las enfermedades con mayor incidencia y mortalidad en la actualidad. Cada tumor se comporta de forma diferente en función del estadío del mismo y del órgano u órganos afectados. Esto ha hecho que haya sido necesario desarrollar diversas líneas de investigación para intentar abordar su curación. Se ha visto que, en el mecanismo de formación y expansión de los tumores neuroepiteliales y mesenquimatosos, puede estar implicada una estructura intermediaria del DNA conocida como unión de Holliday o “Holliday junction”. El objetivo de este trabajo ha sido el de adquirir las competencias teóricas y prácticas necesarias para conseguir cristalizar oligonucleótidos con la unión de Holliday, empleando para ello algunas condiciones que habían demostrado funcionar bien en el pasado. El resultado ha sido exitoso gracias a la obtención de cristales a concentraciones medias de 2-metil-2,4-pentanodiol (MPD), tanto en presencia de cloruro magnésico como de cloruro cálcico. Los resultados obtenidos avalan a la cristalografía como técnica de elucidación estructural de macromoléculas y permiten ser optimistas respecto a la futura obtención de nuevos ligandos que empleen la unión de Holliday como diana terapéutica para tratar estos tipos de cáncer.
Cancer is one of the most important diseases nowadays, with a high incidence and mortality. Each tumour behaves in a different way depending on the stage and the organ or organs affected. For that reason, developing various scientific strategies has been necessary in order to approach a cure. Some studies have proved that a specific DNA structure, known as Holliday junction, is actually involved in formation and growth mechanisms of neuroepitelial and mesenquimal tumours. The main goal to achieve with this paper was the acquierement of enough theoretical and practical knowledge to get crystals from oligonucleotides with the Holliday junction structure, testing some of the conditions that had worked before. We can say, with no doubt, that the project has been successful, because we crystallised the oligos with medium 2-methyl-2,4-pentanediol (MPD) concentrations and both magnesium and calcium chloride. Results have proved that crystallography is a really useful tool to elucidate macromolecular structures and make us feel optimistic about the future discovery of new ligands that may target the Holliday junction and cure these cancers.
Cancer is one of the most important diseases nowadays, with a high incidence and mortality. Each tumour behaves in a different way depending on the stage and the organ or organs affected. For that reason, developing various scientific strategies has been necessary in order to approach a cure. Some studies have proved that a specific DNA structure, known as Holliday junction, is actually involved in formation and growth mechanisms of neuroepitelial and mesenquimal tumours. The main goal to achieve with this paper was the acquierement of enough theoretical and practical knowledge to get crystals from oligonucleotides with the Holliday junction structure, testing some of the conditions that had worked before. We can say, with no doubt, that the project has been successful, because we crystallised the oligos with medium 2-methyl-2,4-pentanediol (MPD) concentrations and both magnesium and calcium chloride. Results have proved that crystallography is a really useful tool to elucidate macromolecular structures and make us feel optimistic about the future discovery of new ligands that may target the Holliday junction and cure these cancers.