1282624-42-3Relevant articles and documents
A BODIPY-Tagged Phosphono Peptide as Activity-Based Probe for Human Leukocyte Elastase
Schulz-Fincke, Anna-Christina,Blaut, Michael,Braune, Annett,Gütschow, Michael
, p. 345 - 350 (2018)
Human leukocyte elastase plays a crucial role in a variety of inflammatory disorders and represents an important subject of biomedical studies. The chemotype of peptidic phosphonates was employed for the design of a new activity-based probe for human leukocyte elastase. Its structure combines the phosphonate warhead with an adequate peptide portion and a BODIPY fluorophore with a clickable ethinylphenyl moiety at meso position. The probe 6 was assembled by copper-catalyzed alkyne-azide 1,3-dipolar cycloaddition. It was characterized as an active site-directed elastase inhibitor exhibiting a second-order rate constant of inactivation of 88400 M-1s-1. The suitability of 6 as a fluorescent probe for human leukocyte elastase was demonstrated by in-gel fluorescence analysis. Labeling experiments and inhibition data toward a panel of related proteases underlined the selectivity of the probe for the targeted leukocyte elastase.
Human neutrophil elastase phosphonic inhibitors with improved potency of action
Winiarski, ?ukasz,Oleksyszyn, Józef,Sieńczyk, Marcin
, p. 6541 - 6553 (2012/09/21)
Herein, we present the synthesis and the measurement of the inhibitory activity of novel peptidyl derivatives of α-aminoalkylphosphonate diaryl esters as human neutrophil elastase inhibitors. Their selectivity against other serine proteases, including porcine pancreatic elastase, chymotrypsin, and trypsin, was also demonstrated. We also describe the preparation of single peptide diastereomers. The most active and selective compound developed possessed a kinact/KI of 2353000 M-1 s -1, which is the most potent irreversible peptidyl inhibitor of human neutrophil elastase reported to date. The peptidyl inhibitors were demonstrated to be stable in PBS buffer and human plasma, as were their complexes with HNE.
Phosphonic pseudopeptides as human neutrophil elastase inhibitors - A combinatorial approach
Sieńczyk, Marcin,Podgórski, Dawid,B?aejewska, Aleksandra,Kulbacka, Julita,Saczko, Jolanta,Oleksyszyn, Józef
, p. 1277 - 1284 (2011/04/12)
Here we present a simple and rapid method for the construction of phosphonic peptide mimetic inhibitor libraries - products of Ugi and Passerini multicomponent condensations - leading to the selection of new biologically active phosphonic pseudopeptides.
Simple phosphonic inhibitors of human neutrophil elastase
Sieńczyk, Marcin,Winiarski, ?ukasz,Kasperkiewicz, Paulina,Psurski, Mateusz,Wietrzyk, Joanna,Oleksyszyn, Józef
, p. 1310 - 1314 (2011/04/16)
Herein, we describe the synthesis and resulting activity of a complex series of α-aminophosphonate diaryl esters as irreversible human neutrophil elastase inhibitors and their selectivity preference for human neutrophil elastase over several other serine proteases such as porcine pancreatic elastase, trypsin, and chymotrypsin. We synthesized and examined the inhibitory potency of several new simple Cbz-protected α- aminoalkylphosphonate diaryl esters that yielded several new HNE inhibitors, where one of the obtained compounds Cbz-ValP(OC6H 4-4-COOMe)2 displayed an apparent second-order inhibition value at 33,015 M-1 s-1.
