The classification of racemases, their diffusion, function, localization, structural features and the state of the art in the discovery of novel drugs targeting such enzymes for the treatment of different pathologies, is discussed. The biological activity of the peptides is found to be strictly dependent, not only on the presence of D-amino acids, but also upon the position of such building blocks along the amino acid sequence. D-amino acids are detected in mammals, including humans, where they play physiological roles of utmost importance. The crystal structure of AlaR from B. stearothermophilus, as well as its complexes with two inhibitors, have been reported and allowed the definition of the active site features. Novel structural information has opened new avenues for the design of specific and potent AlaR inhibitors.
Drug Discovery Targeting Amino Acid Racemases / P. Conti, L. Tamborini, A. Pinto, A. Blondel, P. Minoprio, A. Mozzarelli, C. De Micheli. - In: CHEMICAL REVIEWS. - ISSN 0009-2665. - 111:11(2011 Nov), pp. 6919-6946. [10.1021/cr2000702]
Drug Discovery Targeting Amino Acid Racemases
P. ContiPrimo
;L. TamboriniSecondo
;A. Pinto;C. De Micheli
Ultimo
2011
Abstract
The classification of racemases, their diffusion, function, localization, structural features and the state of the art in the discovery of novel drugs targeting such enzymes for the treatment of different pathologies, is discussed. The biological activity of the peptides is found to be strictly dependent, not only on the presence of D-amino acids, but also upon the position of such building blocks along the amino acid sequence. D-amino acids are detected in mammals, including humans, where they play physiological roles of utmost importance. The crystal structure of AlaR from B. stearothermophilus, as well as its complexes with two inhibitors, have been reported and allowed the definition of the active site features. Novel structural information has opened new avenues for the design of specific and potent AlaR inhibitors.File | Dimensione | Formato | |
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