Peptidomic analysis of blood plasma after in vivo treatment with protease inhibitors--a proof of concept study.
Native peptides can be regarded as surrogate markers for protease activity in biological samples. Analysis of peptides by peptidomics allows to monitor protease activity in vivo and to describe the influence of protease inhibition. To elucidate the potential of peptides as markers for in vivo protease inhibition we analyzed plasma samples from animals treated with either the indirect FXa inhibitor FONDAPARINUX or the dipeptidylpeptidase IV inhibitor AB192. Signals correlating with the treatment were subsequently identified and assessed with respect to protease-dependent consensus cleavage motifs and occurrence of downstream targets. It could be shown that regulated peptides were either substrates, products or downstream targets of the inhibited protease. The results from the present study demonstrate that the in vivo analysis of peptides by peptidomics has the potential to broaden the knowledge of inhibitor related effects in vivo and that this method may pave the way to develop predictive biomarkers.
Tammen
Harald
H
Digilab BioVisioN GmbH, Feodor Lynen Str. 5, 30625 Hannover, Lower Saxony, Germany. h.tammen@peptidomics.de
Hess
Rüdiger
R
Rose
Horst
H
Wienen
Wolfgang
W
Jost
Marco
M
D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005170:Factor X / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D063065:Organophosphonates / Q000494:pharmacology*; D010455:Peptides / Q000097:blood / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
D054873:Dipeptidyl-Peptidase IV Inhibitors; D063065:Organophosphonates; D010455:Peptides; C118220:bis(4-acetamidophenyl) 1-prolylpyrrolidine-2-phosphonate; D005170:Factor X; D011392:Proline; D018819:Dipeptidyl Peptidase 4