{"id":103041,"date":"2025-08-26T08:00:00","date_gmt":"2025-08-26T06:00:00","guid":{"rendered":"https:\/\/www.linseis.com\/sem-categoria\/a-termodinamica-encontra-a-biofarmaceutica-porque-e-que-o-itc-esta-a-tornar-se-cada-vez-mais-relevante-para-os-laboratorios\/"},"modified":"2026-01-12T09:27:50","modified_gmt":"2026-01-12T08:27:50","slug":"a-termodinamica-encontra-a-biofarmaceutica-porque-e-que-o-itc-esta-a-tornar-se-cada-vez-mais-relevante-para-os-laboratorios","status":"publish","type":"post","link":"https:\/\/www.linseis.com\/pt-pt\/conhecimentos\/a-termodinamica-encontra-a-biofarmaceutica-porque-e-que-o-itc-esta-a-tornar-se-cada-vez-mais-relevante-para-os-laboratorios\/","title":{"rendered":"A termodin\u00e2mica encontra a biofarmac\u00eautica &#8211; Porque \u00e9 que o ITC est\u00e1 a tornar-se cada vez mais relevante para os laborat\u00f3rios"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-post\" data-elementor-id=\"103041\" class=\"elementor elementor-103041 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9.317-33.901-.04l-22.667-22.667c-9.373-9.373-9.373-24.569 0-33.941L207.03 130.525c9.372-9.373 24.568-9.373 33.941-.001z\"><\/path><\/svg><\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<div id=\"elementor-toc__4f88904\" class=\"elementor-toc__body\">\n\t\t\t<div class=\"elementor-toc__spinner-container\">\n\t\t\t\t<svg class=\"elementor-toc__spinner eicon-animation-spin e-font-icon-svg e-eicon-loading\" aria-hidden=\"true\" viewBox=\"0 0 1000 1000\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\"><path d=\"M500 975V858C696 858 858 696 858 500S696 142 500 142 142 304 142 500H25C25 237 238 25 500 25S975 237 975 500 763 975 500 975Z\"><\/path><\/svg>\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-a92670d elementor-widget elementor-widget-spacer\" data-id=\"a92670d\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-04a345c elementor-widget elementor-widget-heading\" data-id=\"04a345c\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Introdu\u00e7\u00e3o<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-b22fc03 elementor-widget elementor-widget-text-editor\" data-id=\"b22fc03\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p>No desenvolvimento pr\u00e9-cl\u00ednico de medicamentos, tudo gira em torno da compreens\u00e3o das intera\u00e7\u00f5es moleculares. Quer se trate <b>de complexos prote\u00edna-ligando<\/b>, <b>de liga\u00e7\u00e3o anticorpo-antig\u00e9nio<\/b> ou <b>de intera\u00e7\u00f5es enzima-inibidor<\/b> &#8211; para a sele\u00e7\u00e3o e otimiza\u00e7\u00e3o de princ\u00edpios activos biofarmac\u00eauticos, n\u00e3o se trata apenas de saber se uma mol\u00e9cula se liga, mas tamb\u00e9m de saber como, com que intensidade e porque se liga. <\/p><p>\u00c9 exatamente aqui que entra em jogo <b>a calorimetria de titula\u00e7\u00e3o isot\u00e9rmica (ITC)<\/b>: um m\u00e9todo sem etiquetas que funciona em solu\u00e7\u00e3o para determinar a afinidade de liga\u00e7\u00e3o, <a href=\"https:\/\/www.linseis.com\/messgroessen\/enthalpie\/\" data-auto-event-observed=\"true\">\n  <strong>entalpia (\u0394H)<\/strong>\n<\/a>entropia (\u0394S), a energia livre (\u0394G) e a estequiometria podem ser determinadas numa \u00fanica experi\u00eancia. Torna poss\u00edvel caraterizar as intera\u00e7\u00f5es n\u00e3o s\u00f3 qualitativamente, mas tamb\u00e9m de forma completamente termodin\u00e2mica &#8211; e em condi\u00e7\u00f5es quase fisiol\u00f3gicas. <\/p><p><b>O ITC <\/b>\u00e9 uma ferramenta poderosa para o pessoal de laborat\u00f3rio envolvido na carateriza\u00e7\u00e3o de produtos biol\u00f3gicos, terap\u00eauticas pept\u00eddicas ou prote\u00ednas recombinantes. Nas fases iniciais de rastreio, permite a identifica\u00e7\u00e3o r\u00e1pida de mol\u00e9culas activas de liga\u00e7\u00e3o. Mais tarde, ajuda a otimizar formula\u00e7\u00f5es, validar sistemas tamp\u00e3o ou avaliar par\u00e2metros cr\u00edticos de estabilidade.  <\/p><p>Este artigo destina-se a qualquer pessoa que trabalhe com princ\u00edpios activos biofarmac\u00eauticos no laborat\u00f3rio &#8211; seja em universidades, empresas em fase de arranque ou empresas farmac\u00eauticas estabelecidas. Mostramos como funciona o ITC, quando \u00e9 superior a outros m\u00e9todos e o que deves ter em aten\u00e7\u00e3o para tirares o melhor partido de cada experi\u00eancia. <\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-2a3bb73 elementor-widget elementor-widget-heading\" data-id=\"2a3bb73\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Como funciona a ITC - e porque \u00e9 crucial<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-9873860 elementor-widget elementor-widget-text-editor\" data-id=\"9873860\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p><b>A calorimetria de titula\u00e7\u00e3o isot\u00e9rmica (ITC)<\/b> \u00e9 um dos poucos m\u00e9todos biof\u00edsicos que mede diretamente o calor libertado ou absorvido quando duas mol\u00e9culas se ligam. Ao contr\u00e1rio dos m\u00e9todos espectrosc\u00f3picos ou baseados em etiquetas, como a SPR (espetroscopia de resson\u00e2ncia plasm\u00f3nica de superf\u00edcie) ou a MST (termoforese em microescala), <b>a ITC <\/b>funciona completamente sem etiquetas e em solu\u00e7\u00e3o, o que a torna particularmente atractiva para amostras sens\u00edveis ou nativas. <\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-d7e2d86 elementor-widget elementor-widget-heading\" data-id=\"d7e2d86\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h3 class=\"elementor-heading-title elementor-size-default\">O que acontece na proveta?<\/h3>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-30a2ec8 elementor-widget elementor-widget-text-editor\" data-id=\"30a2ec8\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p>O princ\u00edpio \u00e9 simples mas poderoso: a mol\u00e9cula do analito (por exemplo, uma prote\u00edna) \u00e9 dissolvida numa c\u00e9lula calorim\u00e9trica altamente sens\u00edvel. A mol\u00e9cula ligante (por exemplo, um inibidor ou antig\u00e9nio) \u00e9 titulada atrav\u00e9s de uma seringa fina &#8211; normalmente em 10-20 pequenas injec\u00e7\u00f5es. Cada vez que as mol\u00e9culas se ligam, o calor \u00e9 libertado ou absorvido. Este calor \u00e9 medido pelo dispositivo como um impulso t\u00e9rmico.   <\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-b4b7eba elementor-widget elementor-widget-heading\" data-id=\"b4b7eba\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h3 class=\"elementor-heading-title elementor-size-default\">O que \u00e9 que a ITC realmente produz?<\/h3>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-b992738 elementor-widget elementor-widget-text-editor\" data-id=\"b992738\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p>Uma curva de liga\u00e7\u00e3o \u00e9 calculada a partir dos fluxos de calor para cada inje\u00e7\u00e3o. Isto resulta em <\/p><ul><li><strong>Constante de liga\u00e7\u00e3o (K)<\/strong>: Indica a for\u00e7a da liga\u00e7\u00e3o.<\/li><li><strong>Altera\u00e7\u00e3o de entalpia (\u0394H)<\/strong>: Mostra se a liga\u00e7\u00e3o \u00e9 exot\u00e9rmica ou endot\u00e9rmica.<\/li><li><strong>Mudan\u00e7a de entropia (\u0394S)<\/strong>: Fornece informa\u00e7\u00f5es sobre mudan\u00e7as de ordem no sistema.<\/li><li><strong>Energia livre (\u0394G)<\/strong>: A express\u00e3o termodin\u00e2mica combinada da liga\u00e7\u00e3o.<\/li><li><strong>Par\u00e2metro de estequiometria (n)<\/strong>: Quantos ligandos se ligam por mol\u00e9cula alvo?<\/li><\/ul><p>Estes par\u00e2metros n\u00e3o s\u00f3 ajudam a identificar mol\u00e9culas de sucesso ou l\u00edderes, como tamb\u00e9m fornecem informa\u00e7\u00f5es sobre se a liga\u00e7\u00e3o \u00e9 impulsionada por entropia ou entalpia, o que \u00e9 crucial para a otimiza\u00e7\u00e3o subsequente. Com a sua combina\u00e7\u00e3o de valor informativo, simplicidade e diretriz f\u00edsica, <b>o ITC <\/b>\u00e9 um dos m\u00e9todos mais robustos para caraterizar a liga\u00e7\u00e3o molecular &#8211; especialmente quando \u00e9 importante compreender a base energ\u00e9tica. <\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-b7e9dd8 elementor-widget elementor-widget-heading\" data-id=\"b7e9dd8\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">ITC em uso: aplica\u00e7\u00f5es t\u00edpicas em produtos biofarmac\u00eauticos<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-dfaba7a elementor-widget elementor-widget-text-editor\" data-id=\"dfaba7a\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p>Para muitos no laborat\u00f3rio, coloca-se a quest\u00e3o: quando \u00e9 que vale realmente a pena utilizar as <b>TIC <\/b>?<\/p><p>A resposta: Sempre que o objetivo n\u00e3o \u00e9 apenas detetar liga\u00e7\u00f5es, mas compreend\u00ea-las em pormenor. A calorimetria de titula\u00e7\u00e3o isot\u00e9rmica n\u00e3o s\u00f3 fornece valores para as constantes de liga\u00e7\u00e3o para quest\u00f5es biofarmac\u00eauticas, como tamb\u00e9m oferece conhecimentos termodin\u00e2micos profundos que s\u00e3o cruciais para a carateriza\u00e7\u00e3o e otimiza\u00e7\u00e3o de ingredientes activos. <\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-72b3d3e elementor-widget elementor-widget-heading\" data-id=\"72b3d3e\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h3 class=\"elementor-heading-title elementor-size-default\">Intera\u00e7\u00f5es prote\u00edna-ligando: O cl\u00e1ssico<\/h3>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-cca05d2 elementor-widget elementor-widget-text-editor\" data-id=\"cca05d2\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p>Na investiga\u00e7\u00e3o inicial de medicamentos, em particular, o objetivo \u00e9 identificar os parceiros de liga\u00e7\u00e3o, quantificar a sua afinidade e decidir se uma estrutura principal tem potencial. O <b>ITC <\/b>pode ser utilizado para: <\/p><ul><li>Testa pequenas mol\u00e9culas (por exemplo, inibidores) contra enzimas ou prote\u00ednas de transporte<\/li><li>Investiga\u00e7\u00e3o dos princ\u00edpios activos dos p\u00e9ptidos e da sua liga\u00e7\u00e3o ao alvo<\/li><li>Dete\u00e7\u00e3o energ\u00e9tica de altera\u00e7\u00f5es conformacionais durante a liga\u00e7\u00e3o<\/li><\/ul>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-6ba7a57 elementor-widget elementor-widget-heading\" data-id=\"6ba7a57\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h3 class=\"elementor-heading-title elementor-size-default\">Intera\u00e7\u00f5es anticorpo-antig\u00e9nio: Compreender a afinidade, n\u00e3o apenas medi-la<\/h3>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-77b32c1 elementor-widget elementor-widget-text-editor\" data-id=\"77b32c1\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p>O m\u00e9todo fornece resultados para s\u00f3lidos e l\u00edquidos, bem como para p\u00f3s e pastas, com elevada precis\u00e3o de medi\u00e7\u00e3o, o que o torna particularmente valioso para o desenvolvimento de materiais de el\u00e9ctrodos inovadores.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-be0b508 elementor-widget elementor-widget-heading\" data-id=\"be0b508\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h3 class=\"elementor-heading-title elementor-size-default\">Considera\u00e7\u00f5es espec\u00edficas do material e efeitos do envelhecimento<\/h3>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-4451a72 elementor-widget elementor-widget-text-editor\" data-id=\"4451a72\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p><b>A ITC <\/b>\u00e9 um complemento valioso para o desenvolvimento de terap\u00eauticas baseadas em anticorpos:<\/p><ul><li>Medi\u00e7\u00e3o precisa da entalpia e entropia das liga\u00e7\u00f5es (\u2192 impress\u00f5es digitais termodin\u00e2micas)<\/li><li>Avalia\u00e7\u00e3o da estequiometria (por exemplo, liga\u00e7\u00e3o monovalente vs. bivalente)<\/li><li>Compara\u00e7\u00e3o de variantes de anticorpos nativos e modificados em tamp\u00e3o ou soro<\/li><\/ul><p>Isto n\u00e3o s\u00f3 permite a sele\u00e7\u00e3o dos melhores candidatos de liga\u00e7\u00e3o, como tamb\u00e9m permite tirar conclus\u00f5es sobre ep\u00edtopos e mecanismos de liga\u00e7\u00e3o.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-e16a591 elementor-widget elementor-widget-heading\" data-id=\"e16a591\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h3 class=\"elementor-heading-title elementor-size-default\">Desenvolvimento de formula\u00e7\u00f5es: an\u00e1lise de tamp\u00f5es e de estabilidade<\/h3>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-b94fc90 elementor-widget elementor-widget-text-editor\" data-id=\"b94fc90\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p><b>O ITC <\/b>tamb\u00e9m pode ser informativo sem liga\u00e7\u00e3o de ligandos &#8211; por exemplo, para an\u00e1lise:<\/p><ul><li>Sele\u00e7\u00e3o do tamp\u00e3o (por exemplo, se o pr\u00f3prio tamp\u00e3o interage com a prote\u00edna)<\/li><li>da estabilidade t\u00e9rmica atrav\u00e9s das chamadas experi\u00eancias de &#8220;calor de dilui\u00e7\u00e3o<\/li><li>de sistemas auto-associados (por exemplo, agrega\u00e7\u00e3o, dimeriza\u00e7\u00e3o).<\/li><\/ul><p>Um exemplo da pr\u00e1tica:  <strong> <\/strong>Num estudo, <b>o ITC <\/b>foi utilizado para testar prote\u00ednas recombinantes em diferentes formula\u00e7\u00f5es. Isto revelou n\u00e3o s\u00f3 diferen\u00e7as na afinidade de liga\u00e7\u00e3o, mas tamb\u00e9m indica\u00e7\u00f5es de instabilidades estruturais &#8211; muito antes de ocorrerem agrega\u00e7\u00f5es vis\u00edveis. <\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-8d90305 elementor-widget elementor-widget-spacer\" data-id=\"8d90305\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-00f172b elementor-widget elementor-widget-heading\" data-id=\"00f172b\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Conclus\u00e3o<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-260a773 elementor-widget elementor-widget-text-editor\" data-id=\"260a773\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p><b>O ITC <\/b>fornece dados precisos, robustos e aprofundados que os m\u00e9todos convencionais muitas vezes n\u00e3o oferecem, ou oferecem apenas indiretamente. Para os utilizadores do laborat\u00f3rio, isto significa: uma ferramenta que poupa tempo, protege as experi\u00eancias e permite decis\u00f5es bem fundamentadas. <\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-a3e594d elementor-widget elementor-widget-spacer\" data-id=\"a3e594d\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-efce10d elementor-widget elementor-widget-text-editor\" data-id=\"efce10d\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p><strong>Bibliografia<\/strong><\/p><p>[1] V. Linkuviene, G. Krainer, W.-Y. Chen, D. Matulis, Calorimetria de titula\u00e7\u00e3o isot\u00e9rmica para o design de medicamentos: Precis\u00e3o das medi\u00e7\u00f5es de entalpia e constante de liga\u00e7\u00e3o e compara\u00e7\u00e3o dos instrumentos, Bioqu\u00edmica Anal\u00edtica 515, 61-64, 2016<\/p><p>[2] H. Su, Y. Xu, Aplica\u00e7\u00e3o da carateriza\u00e7\u00e3o baseada em ITC da associa\u00e7\u00e3o termodin\u00e2mica e cin\u00e9tica de ligandos com prote\u00ednas no design de medicamentos, Frontiers in Pharmacology 9, 1133, 2018<\/p><p>[3] L. Baranauskiene, T.-C. Kuo, W.-Y. Chen, D. Matulis, Calorimetria de titula\u00e7\u00e3o isot\u00e9rmica para carateriza\u00e7\u00e3o de prote\u00ednas recombinantes, Opini\u00e3o Atual em Biotecnologia 55, 9-15, 2019<\/p><p>[4] N. L. Traulsen, Thermodynamic analysis of supramolecules by isothermal titration calorimetry, dissertation, 2015, Freie Universit\u00e4t Berlin<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-5d88101 elementor-widget elementor-widget-html\" data-id=\"5d88101\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"html.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<script type=\"application\/ld+json\">{\r\n  \"@context\": \"https:\/\/schema.org\",\r\n  \"@type\": \"FAQPage\",\r\n  \"mainEntity\": [{\r\n    \"@type\": \"Question\",\r\n    \"name\": \"Welche Parameter k\u00f6nnen mit der isothermen Titrationskalorimetrie (ITC) in einem einzigen Experiment bestimmt werden?\",\r\n    \"acceptedAnswer\": {\r\n      \"@type\": \"Answer\",\r\n      \"text\": \"Genau hier kommt die isotherme Titrationskalorimetrie (ITC) ins Spiel: eine label-freie, in L\u00f6sung arbeitende Methode, mit der sich Bindungsaffinit\u00e4t, Enthalpie (\u0394H), Entropie (\u0394S), freie Energie (\u0394G) und St\u00f6chiometrie in einem einzigen Experiment bestimmen lassen.\"\r\n    }\r\n  },{\r\n    \"@type\": \"Question\",\r\n    \"name\": \"Warum ist die ITC f\u00fcr Labormitarbeiter in der biopharmazeutischen Forschung ein wichtiges Werkzeug?\",\r\n    \"acceptedAnswer\": {\r\n      \"@type\": \"Answer\",\r\n      \"text\": \"F\u00fcr Labormitarbeiter, die mit der Charakterisierung von Biologika, Peptidtherapeutika oder rekombinanten Proteinen befasst sind, ist die ITC ein m\u00e4chtiges Werkzeug. In fr\u00fchen Screening-Phasen erlaubt sie, bindungsaktive Molek\u00fcle schnell zu identifizieren. Sp\u00e4ter hilft sie, Formulierungen zu optimieren, Puffersysteme zu validieren oder kritische Stabilit\u00e4tsparameter zu bewerten.\"\r\n    }\r\n  },{\r\n    \"@type\": \"Question\",\r\n    \"name\": \"Worin unterscheidet sich die isotherme Titrationskalorimetrie (ITC) von spektroskopischen oder markierungsbasierten Methoden?\",\r\n    \"acceptedAnswer\": {\r\n      \"@type\": \"Answer\",\r\n      \"text\": \"Im Gegensatz zu spektroskopischen oder markierungsbasierten Methoden wie SPR (Oberfl\u00e4chenplasmonenresonanzspektroskopie) oder MST (Microscale Thermophorese) arbeitet die ITC vollkommen label-frei und in L\u00f6sung, was sie besonders attraktiv f\u00fcr empfindliche oder native Proben macht.\"\r\n    }\r\n  },{\r\n    \"@type\": \"Question\",\r\n    \"name\": \"Welche Parameter lassen sich aus den W\u00e4rmefl\u00fcssen bei einer ITC-Messung berechnen?\",\r\n    \"acceptedAnswer\": {\r\n      \"@type\": \"Answer\",\r\n      \"text\": \"Aus den W\u00e4rmefl\u00fcssen bei jeder Injektion wird eine Bindungskurve berechnet. Daraus ergeben sich: 1. Bindungskonstante (K): Gibt an, wie stark die Bindung ist. 2. Enthalpie\u00e4nderung (\u0394H): Zeigt, ob die Bindung exotherm oder endotherm ist. 3. Entropie\u00e4nderung (\u0394S): Gibt Aufschluss \u00fcber Ordnungs\u00e4nderungen im System. 4. Freie Energie (\u0394G): Der kombinierte thermodynamische Ausdruck der Bindung. 5. St\u00f6chiometrieparameter (n): Wie viele Liganden binden pro Target-Molek\u00fcl?\"\r\n    }\r\n  },{\r\n    \"@type\": \"Question\",\r\n    \"name\": \"Wann lohnt sich der Einsatz von ITC wirklich?\",\r\n    \"acceptedAnswer\": {\r\n      \"@type\": \"Answer\",\r\n      \"text\": \"Immer dann, wenn es darum geht, Bindungen nicht nur nachzuweisen, sondern im Detail zu verstehen. Die isotherme Titrationskalorimetrie liefert f\u00fcr biopharmazeutische Fragestellungen nicht nur Werte f\u00fcr die Bindungskonstanten, sondern bietet tiefe thermodynamische Einblicke, die f\u00fcr die Wirkstoffcharakterisierung und -optimierung entscheidend sind.\"\r\n    }\r\n  },{\r\n    \"@type\": \"Question\",\r\n    \"name\": \"Welche zus\u00e4tzlichen Fragestellungen lassen sich mit der ITC auch ohne Ligandenbindung untersuchen?\",\r\n    \"acceptedAnswer\": {\r\n      \"@type\": \"Answer\",\r\n      \"text\": \"Die ITC kann auch ohne Ligandenbindung aufschlussreich sein \u2013 etwa zur Analyse: 1. von Pufferauswahl (z. B. ob ein Puffer selbst mit dem Protein interagiert) 2. von thermischer Stabilit\u00e4t \u00fcber sogenannte \u201eheat of dilution\u201c-Experimente 3. von selbstassoziierenden Systemen (z. B. Aggregation, Dimerisierung).\"\r\n    }\r\n  }]\r\n}\r\n<\/script>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"<p>No desenvolvimento pr\u00e9-cl\u00ednico de medicamentos, tudo gira em torno da compreens\u00e3o das intera\u00e7\u00f5es moleculares. Quer se trate de complexos prote\u00edna-ligando, de liga\u00e7\u00e3o anticorpo-antig\u00e9nio ou de intera\u00e7\u00f5es enzima-inibidor &#8211; para a sele\u00e7\u00e3o e otimiza\u00e7\u00e3o de princ\u00edpios activos biofarmac\u00eauticos, n\u00e3o se trata apenas de saber se uma mol\u00e9cula se liga, mas tamb\u00e9m de saber como, com que intensidade e porque se liga. <\/p>\n","protected":false},"author":3,"featured_media":95696,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"categories":[654],"tags":[],"class_list":["post-103041","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-conhecimentos"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.linseis.com\/pt-pt\/wp-json\/wp\/v2\/posts\/103041","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.linseis.com\/pt-pt\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.linseis.com\/pt-pt\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.linseis.com\/pt-pt\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.linseis.com\/pt-pt\/wp-json\/wp\/v2\/comments?post=103041"}],"version-history":[{"count":0,"href":"https:\/\/www.linseis.com\/pt-pt\/wp-json\/wp\/v2\/posts\/103041\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.linseis.com\/pt-pt\/wp-json\/wp\/v2\/media\/95696"}],"wp:attachment":[{"href":"https:\/\/www.linseis.com\/pt-pt\/wp-json\/wp\/v2\/media?parent=103041"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.linseis.com\/pt-pt\/wp-json\/wp\/v2\/categories?post=103041"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.linseis.com\/pt-pt\/wp-json\/wp\/v2\/tags?post=103041"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}