Article ID: CBB320500524

Cristalización de proteínas en el diseño de fármacos en los últimos 50 años (2015)

unapi

ABSTRACT We live in an era where we expect to be able to visit our doctor and obtain a pill to cure any ailment from which we suffer. Yet, this is still not the case. Many of the current cures are still derived from natural sources although new drugs are increasingly the result of intelligent design. In this process, X-ray protein crystallography now plays a major and effective role in the discovery of new treatments. The developments that have made this possible have evolved during the past fifty years. The methods for crystallizing macromolecules and determining their structures by X-ray crystallography have been automated and the speed for X-ray data acquisition is several orders of magnitude faster. Fifty years ago it took several years to solve a single structure. Now, several protein–ligand complexes can be determined in single day. High-throughput crystallography is considered to be a great asset to the drug discovery process, providing a fast way to tailor drug candidates to their targets by analysing their binding mode in detail. Crystallization remains the main challenge. RESUMEN Vivimos en una época en la que esperamos ir al médico y obtener una pastilla para curar cualquier dolencia que padezcamos; por desgracia, esta expectativa no es real. Aunque muchos de los remedios en uso provienen de fuentes naturales, la mayoría de los nuevos medicamentos son el resultado de la investigación científica. En el proceso de diseño y descubrimiento de fármacos, la cristalografía de proteínas juega un papel central. Los conocimientos que han hecho esto posible han venido evolucionando desde hace cincuenta años aproximadamente. Los métodos de cristalización de macromoléculas y la determinación de sus estructuras a través de la cristalografía de rayos X han sido automatizados y miniaturizados y la velocidad de la adquisición de datos de difracción ha aumentado en varios órdenes de magnitud. Si hace cincuenta años la resolución de una sola estructura podría llevar varios años, actualmente se pueden determinar las estructuras de varios complejos proteína-ligando en un solo día. La cristalografía de alto rendimiento hoy día es un gran recurso en el proceso del descubrimiento de fármacos pues proporciona una manera rápida y precisa de adaptar los fármacos candidatos a las dianas mediante el análisis de su modo de unión. La cristalización sigue siendo el principal desafío.

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Authors & Contributors
Irish, Stephen T.
Sanz-Aparicio, Julia
Adams, Paul D.
Urzhumtsev, Alexandre
Abad-Zapatero, Celerino
Afonine, Pavel V.
Journals
Arbor: Ciencia, Pensamiento y Cultura
Ambix: Journal of the Society for the History of Alchemy and Chemistry
Leonardo
Substantia: An International Journal of the History of Chemistry
Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences
Notes and Records: The Royal Society Journal of the History of Science
Publishers
Prometheus Books
Oxford University Press
Princeton University
Concepts
Crystallography
Chemistry
X-ray crystallography
Physics
Biology
Science and art
People
Hodgkin, Dorothy Crowfoot
Wohlwill, Emil
Smithson, James
Naumann, Carl Friedrich
Mitscherlich, Eilhard
Laue, Max von
Time Periods
20th century
19th century
20th century, early
18th century
17th century
Places
Great Britain
Spain
Germany
Europe
Institutions
American Institute of Physics
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