2024-03-29T00:34:32Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1120912020-05-11T09:58:53Zcom_10261_52707com_10261_5col_10261_52715
Design and synthesis of fungical transglycosidase inhibitors
Gomollón-Bel, Fernando
Marca, Eduardo
Hurtado-Guerrero, Ramón
Delso, J. Ignacio
Tejero, Tomás
Merino, Pedro
Consejo Superior de Investigaciones Científicas (España)
Fundación Agencia Aragonesa para la Investigación y el Desarrollo
Trabajo presentado al 15th JCF Frühjahrssymposium (Congreso de Jóvenes Investigadores de la Sociedad Alemana de Química) celebrado en Berlín (Alemania) del 6 al 9 de marzo de 2013.
Transglycosydases are a group of key enzymes in preserving the structure of the cell-wall in most fungi. Therefore, the study of their active site and preparation of inhibitors could lead to the obtention of powerful fungicides which could be active against infectious organisms such as Aspergillus fumigatus or Candida albicans. We were able to study the x-ray crystalline structure of Gas2, a membrane bound enzyme from Saccharomices cerevisae, a fungus that is usually studied in Biochemistry because of its genetical and structural analogies to pathogens like A. fumigatus and C. albicans. Knowing the active site and the optimal substrate for the enzyme, molecular docking studies were carried out to design the target molecules to be synthesized. We have optimized a purification method of β(1,3)-oligosaccharides from commercially available glucans and we have studied the synthesis of cyclic six membered nitrones that can be functionalized with hydrophobic substituents (R) which will be able to fit in a lipophilic cavity close to Gas2 active site. Nowadays, new docking, molecular dynamics and inhibition studies are being carried out to determine the activity as fungicides of the prepared compounds.
F. G.-B. thanks the Spanish Council for Scientific Research (CSIC) for a JAE-Predoctoral grant. R. H.-G. thanks the ARAID Foundation for a permanent position.
Peer Reviewed
2015-03-10T11:29:56Z
2015-03-10T11:29:56Z
2013
2015-03-10T11:29:57Z
comunicación de congreso
http://purl.org/coar/resource_type/c_5794
15th JCF-Frühjahrssymposium (2013)
http://hdl.handle.net/10261/112091
http://dx.doi.org/10.13039/501100003339
http://dx.doi.org/10.13039/501100008767
Sí
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