biostudies-literatureUnknown9(4)Schulz-Fincke ACHuman 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 experimentACS medicinal chemistry letters345-350https://www.ebi.ac.uk/biostudies/studies/S-EPMC5900331biostudies-literatureA BODIPY-Tagged Phosphono Peptide as Activity-Based Probe for Human Leukocyte Elastase.PMC5900331Gutschow MBraune ASchulz-Fincke ACBlaut MfalseA BODIPY-Tagged Phosphono Peptide as Activity-Based Probe for Human Leukocyte Elastase.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 experiment2018-01-01T00:00:00Z2018 Apr2025-05-29T22:16:47.821Z2025-05-29T22:16:47.821ZS-EPMC59003312967069810.1021/acsmedchemlett.7b00533