{"id":68063,"date":"2018-03-09T22:56:30","date_gmt":"2018-03-09T22:56:30","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/2-alquil-2-carboxiazetidinas-como-inductores-de-giros-inversos-analisis-y-aplicacion-a-la-sa%c2%adntesis-de-mimeticos-de-neurotrofinas\/"},"modified":"2018-03-09T22:56:30","modified_gmt":"2018-03-09T22:56:30","slug":"2-alquil-2-carboxiazetidinas-como-inductores-de-giros-inversos-analisis-y-aplicacion-a-la-sa%c2%adntesis-de-mimeticos-de-neurotrofinas","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/propiedades-de-materiales\/2-alquil-2-carboxiazetidinas-como-inductores-de-giros-inversos-analisis-y-aplicacion-a-la-sa%c2%adntesis-de-mimeticos-de-neurotrofinas\/","title":{"rendered":"2-alquil-2-carboxiazetidinas como inductores de giros inversos: an\u00e1lisis y aplicaci\u00f3n a la s\u00edntesis de mim\u00e9ticos de neurotrofinas"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Jos\u00e9 Luis Baeza Garc\u00eda <\/strong><\/h2>\n<p>Esta tesis se ha centrado en el estudio de esqueletos capaces de inducir giros inversos como una herramienta \u00fatil en el dise\u00f1o de moduladores de interacciones prote\u00edna-prote\u00edna y prote\u00edna-p\u00e9ptido. en el primer cap\u00edtulo se estudia la capacidad inductora de giros inversos de una serie de 2-alquil-2-carboxiazetidinas cuando se incorporan en p\u00e9ptidos peque\u00f1os. En concreto, se eligieron derivados dipept\u00eddicos con un grupo acilo o aciloxi en posici\u00f3n n-terrninal y un agrupamiento n-metilcarboxamida en c-terminal, como modelos tetrapept\u00eddicos sencillos (r-co-xaa-yaa-nh-me). El residuo de azetidina se incorpor\u00f3 tanto en la posici\u00f3n i+1 como en la i+2. A efectos comparativos tambi\u00e9n se sustituyeron estas posiciones con derivados de prolina, que poseen capacidad para inducir giros beta. El an\u00e1lisis conformacional se realiz\u00f3 mediante estudios de modelizaci\u00f3n molecular, ir, rmn y rayos x. Los resultados de estos estudios han apoyado la capacidad inductora de giros gamma de los derivados de azetidinas, por lo que estos derivados se podr\u00edan aplicar al estudio de la conformaci\u00f3n bioactiva de p\u00e9ptidos, a la vez que ser\u00edan esqueletos \u00fatiles para la obtenci\u00f3n de an\u00e1logos de p\u00e9ptidos de inter\u00e9s biol\u00f3gico. En el segundo cap\u00edtulo de la tesis se aborda el dise\u00f1o, s\u00edntesis y evaluaci\u00f3n biol\u00f3gica de mim\u00e9ticos de fragmentos importantes para la actividad de p\u00e9ptidos bioactivos con estructura de giro inverso. En concreto, se centra en una serie de loops del factor de crecimiento nervioso (ngf) y el factor de crecimiento derivado de cerebro (bdnf). As\u00ed, se dise\u00f1aron una serie de an\u00e1logos lineales de los loops 1 y 4 de ngf, que incorporan amino\u00e1cidos conformacionalmente restringidos capaces de inducir giros inversos en posiciones i+1 e i+2. En relaci\u00f3n a los mim\u00e9ticos de bdnf, se han dise\u00f1ado una serie de an\u00e1logos c\u00edclicos de los loops 2 y 4. Para este fin se realizaron estudios de modelizaci\u00f3n molecular para seleccionar espaciadores adecuados para unir los amino \u00e1cidos n- y c- terminales de estos loops. Es de se\u00f1alar, que tres de los an\u00e1logos c\u00edclicos de bdnf han sido capaces de inhibir la fosforilaci\u00f3n inducida por bdnf en sus receptores.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>2-alquil-2-carboxiazetidinas como inductores de giros inversos: an\u00e1lisis y aplicaci\u00f3n a la s\u00edntesis de mim\u00e9ticos de neurotrofinas<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 2-alquil-2-carboxiazetidinas como inductores de giros inversos: an\u00e1lisis y aplicaci\u00f3n a la s\u00edntesis de mim\u00e9ticos de neurotrofinas <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Jos\u00e9 Luis Baeza Garc\u00eda <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Aut\u00f3noma de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 18\/11\/2008<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Mercedes Mart\u00edn Mart\u00ednez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Jos\u00e9 Luis Garc\u00eda ruano <\/li>\n<li>david Andreu mart\u00ednez (vocal)<\/li>\n<li>sonsoles Vel\u00e1zquez d\u00edaz (vocal)<\/li>\n<li>Mar\u00eda \u00e1ngeles Jim\u00e9nez l\u00f3pez (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Jos\u00e9 Luis Baeza Garc\u00eda Esta tesis se ha centrado en el estudio de esqueletos capaces de inducir [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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