Potent new leucine aminopeptidase inhibitor of novel structure synthesised by a modified Wadsworth-Emmons (Horner) Wittig procedure.
The use of a leucine-derived alpha-keto-beta-aldehyde (glyoxal) as a substrate in the Horner-Emmons (Wadsworth) Wittig reaction has enabled the synthesis of (Z)-7-methyl-5(S)-amino-4-oxo-methyl-oct-2-eneoate. This novel compound is a potent inhibitor (Ki = 76 nM) of leucine aminopeptidase and provides an interesting new template for the development of metallopeptidase inhibitors.
Walker
B
B
Division of Biomedicinal Chemistry, School of Pharmacy, The Queen's University of Belfast, Medical Biology Centre, UK. brian.walker@qub.ac.uk
Darkins
P A
PA
McKervey
M A
MA
Moncrieff
H M
HM
Lynas
J F
JF
D002625:Chemistry, Organic / Q000379:methods; D006037:Glyoxal / Q000737:chemistry*; D007931:Leucyl Aminopeptidase / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology
D011480:Protease Inhibitors; D006037:Glyoxal; D007931:Leucyl Aminopeptidase