Abstract
Electrospray ionization mass spectrometry was used to investigate the mechanism of inhibition of porcine pancreatic
elastase (PPE) by two cephalosporins, L-658758 [1-[[3-(acetoxymethyl)-7a-methoxy-8-oxo-5-thia-1-azabicyclo[4.2.0.]oct-
2-en-2-yl]carbonyl]proline S,S dioxide], and L-647957 [1-[[3-(acetoxymethyl)-7a-chloro-8-oxo-5-thia-1-
azabicyclo[4.2.0.]oct-2-en-2-yl]carboxylic tbutyl ester]S,S dioxide]. The mass shifts, obsd. as compared with native PPE,
upon incubation with the inhibitors were consistent with the formation of an acyl enzyme complex followed by expulsion
of the acetoxy group from the 3'-methylene position of the cephalosporin inhibitors. In the case of L-647957 the mass
shifts also indicated loss of HCl. In contrast for L-658758, no evidence was accrued for loss of methanol, consistent with
previous kinetic studies on human leukocyte elastase.
elastase (PPE) by two cephalosporins, L-658758 [1-[[3-(acetoxymethyl)-7a-methoxy-8-oxo-5-thia-1-azabicyclo[4.2.0.]oct-
2-en-2-yl]carbonyl]proline S,S dioxide], and L-647957 [1-[[3-(acetoxymethyl)-7a-chloro-8-oxo-5-thia-1-
azabicyclo[4.2.0.]oct-2-en-2-yl]carboxylic tbutyl ester]S,S dioxide]. The mass shifts, obsd. as compared with native PPE,
upon incubation with the inhibitors were consistent with the formation of an acyl enzyme complex followed by expulsion
of the acetoxy group from the 3'-methylene position of the cephalosporin inhibitors. In the case of L-647957 the mass
shifts also indicated loss of HCl. In contrast for L-658758, no evidence was accrued for loss of methanol, consistent with
previous kinetic studies on human leukocyte elastase.
| Original language | English |
|---|---|
| Journal | Tetrahedron |
| DOIs | |
| Publication status | Published - 1993 |