Metalloproteases see the light.

Nature Chemical Biology (Impact Factor: 13.22). 06/2006; 2(5):229-30. DOI: 10.1038/nchembio0506-229
Source: PubMed
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    ABSTRACT: Non-steroidal anti-inflammatory drugs and aureolic acid group of anti-cancer drugs belong to the class of generic drugs. Research with some members of these two groups of drugs in different laboratories has unveiled functions other than those for which they were primarily developed as drugs. Here we have reviewed the molecular mechanism behind the multiple functions of these drugs that might lead to employ them for treatment of diseases in addition to those they are presently employed. The distinct advantage of using old drugs for alternate functions lies in their well-studied Absorption Distribution Metabolism Excretion and Toxicity (ADMET) profile.
    Recent Advances in Medicinal Chemistry, First edited by Atta-ur-Rahman, Muhammad Iqbal Choudhary, George Perry, 08/2014: chapter 1: pages 3-55; Bentham Science., ISBN: 978-1-60805-797-9
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    ABSTRACT: Aminopeptidases process the N-terminal amino acids of target substrates by sequential cleavage of one residue at a time. They are found in all cell compartments of prokaryotes and eukaryotes, being implicated in the major proteolytic events of cell survival, defense, growth, and development. We present a new approach for the fast and reliable evaluation of the substrate specificity of individual aminopeptidases. Using solid phase chemistry with the 7-amino-4-carbamoylmethylcoumarin fluorophore, we have synthesized a library of 61 individual natural and unnatural amino acids substrates, chosen to cover a broad spectrum of the possible interactions in the S1 pocket of this type of protease. As proof of concept, we determined the substrate specificity of human, pig, and rat orthologs of aminopeptidase N (CD13), a highly conserved cell surface protease that inactivates enkephalins and other bioactive peptides. Our data reveal a large and hydrophobic character for the S1 pocket of aminopeptidase N that is conserved with aminopeptidase Ns. Our approach, which can be applied in principle to all aminopeptidases, yields useful information for the design of specific inhibitors, and more importantly, reveals a relationship between the kinetics of substrate hydrolysis and the kinetics of enzyme inhibition.
    Journal of Biological Chemistry 11/2009; 285(5):3310-8. DOI:10.1074/jbc.M109.060418 · 4.60 Impact Factor

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