Inhibition of dipeptidyl peptidase IV (CD26) by peptide boronic acid dipeptides.
Peptide boronic acid dipeptide compounds were analyzed for their ability to inhibit recombinant human dipeptidylpeptidase IV (CD26, DPPIV). Rate constants for the peptide boronates are difficult to obtain because the active boronic acid dipeptide exists in equilibrium with a cyclic inactive species in aqueous solution. Rate constants were determined for the inhibition of DPPIV using several peptide boronates at different pH values. Val-boroPro forms the most tightly bound complex with DPPIV; the first order half life for dissociation of the inactive enzyme-inhibitor complex at 23 degrees C is approximately 27 days.
Pargellis
C A
CA
Department of Biochemistry, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT 06877, USA.
Campbell
S J
SJ
Pav
S
S
Graham
E T
ET
Pitner
T P
TP
D001667:Binding, Competitive; D001897:Boronic Acids / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence
D001897:Boronic Acids; D004151:Dipeptides; D015842:Serine Proteinase Inhibitors; D018819:Dipeptidyl Peptidase 4