Sniffing out the culprits of dust allergies

There is increasing evidence suggesting that allergic-response diseases such as asthma, perennial rhinitis, and atopic dermatitis result from proteolytic or other enzymatic activity in common allergens. Dust is commonly allergenic, and to investigate the presence of active proteases in dust, researchers led by Jennifer Harris at The Scripps Research Institute and Nicolas Winssinger at the Université Louis Pasteur examined an extract derived from dust mites. The researchers devised and used a novel combined-library approach for this purpose--a method that enabled simultaneous identification of proteases from complex samples and isolation of protease-specific inhibitors. In this way, Der 1 p was identified as an active cysteine protease in dust mite extracts, and a Der 1 p-specific small-molecule inhibitor was isolated from a peptide nucleic acid (PNA)-encoded small-molecule library. As a result of this investigation, Der 1 p was implicated in the cleavage of the CD4+ T cell receptor CD25--the Der 1 p inhibitor has a dose-dependent ability to protect the receptor on whole cells. This study demonstrates the utility of this new approach for quickly identifying active proteases involved in allergic responses or other disease processes and effective inhibitors that can be further developed for diagnostic or therapeutic research.

Nicolas Winssinger, Robert Damoiseaux, David C. Tully, Bernhard H. Geierstanger, Keith Burdick, and Jennifer L. Harris: "PNA-Encoded Protease Substrate Microarrays"

Jennifer Harris, Daniel E. Mason, Jun Li, Keith W. Burdick, Bradley J. Backes, Teresa Chen, Aaron Shipway, Gino Van Heeke, Lucy Gough, Amir Ghaemmaghami, Farouk Shakib, Francois Debaene, and Nicolas Winssinger: "Activity Profile of Dust Mite Allergen Extract Using Substrate Libraries and Functional Proteomic Microarrays"

Published in Chemistry & Biology, Volume 11, Number 10, October 2004, pages 1351–1360 and 1361–1372.

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