Unusual activity pattern of leucine aminopeptidase inhibitors based on phosphorus containing derivatives of methionine and norleucine
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Enzyme Activation drug effects MeSH
- Phosphorus chemistry MeSH
- Enzyme Inhibitors pharmacology MeSH
- Kidney enzymology MeSH
- Leucyl Aminopeptidase antagonists & inhibitors MeSH
- Methionine * chemistry pharmacology MeSH
- Molecular Structure MeSH
- Norleucine * chemistry pharmacology MeSH
- Swine MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Phosphorus MeSH
- Enzyme Inhibitors MeSH
- Leucyl Aminopeptidase MeSH
- Methionine * MeSH
- Norleucine * MeSH
Ligands containing bulky aliphatic P1 residues exhibit a high affinity towards cytosolic leucine aminopeptidase, a bizinc protease of biomedical significance. According to this specificity, a series of phosphonic and phosphinic compounds have been put forward as novel putative inhibitors of the enzyme. These phosphonic and phosphinic compounds were derivatives of methionine and norleucine as both single amino acids and dipeptides. The designed inhibitors were synthesised and tested towards the peptidase isolated from porcine kidneys using an improved separation procedure affording superior homogeneity. Unexpectedly, organophosphorus derivatives of methionine and norleucine exhibited moderate activity with K(i) values in the micromolar range.
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