Drug screening strategy for human membrane proteins: from NMR protein backbone structure to in silica- and NMR-screened hits.
Biochem Biophys Res Commun
; 445(4): 724-33, 2014 Mar 21.
Article
em En
| MEDLINE
| ID: mdl-24525125
ABSTRACT
About 8000 genes encode membrane proteins in the human genome. The information about their druggability will be very useful to facilitate drug discovery and development. The main problem, however, consists of limited structural and functional information about these proteins because they are difficult to produce biochemically and to study. In this paper we describe the strategy that combines Cell-free protein expression, NMR spectroscopy, and molecular DYnamics simulation (CNDY) techniques. Results of a pilot CNDY experiment provide us with a guiding light towards expedited identification of the hit compounds against a new uncharacterized membrane protein as a potentially druggable target. These hits can then be further characterized and optimized to develop the initial lead compound quicker. We illustrate such "omics" approach for drug discovery with the CNDY strategy applied to two example proteins hypoxia-induced genes HIGD1A and HIGD1B.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
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Ressonância Magnética Nuclear Biomolecular
/
Proteínas de Membrana
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Proteínas de Neoplasias
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos