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Diarylethene-Based Photoswitchable Inhibitors of Serine Proteases

Babii, Oleg 1,2; Afonin, Sergii 1; Diel, Christian 3; Huhn, Marcel 3; Dommermuth, Jennifer 3; Schober, Tim 3; Koniev, S.; Hrebonkin, Andrii 1; Nesterov-Mueller, Alexander 2; Komarov, I. V.; Ulrich, Anne S. 1,3
1 Institut für Biologische Grenzflächen (IBG), Karlsruher Institut für Technologie (KIT)
2 Institut für Mikrostrukturtechnik (IMT), Karlsruher Institut für Technologie (KIT)
3 Institut für Organische Chemie (IOC), Karlsruher Institut für Technologie (KIT)

Abstract:

A bicyclic peptide scaffold was chemically adapted to generate diarylethene-based photoswitchable inhibitors of serine protease Bos taurus trypsin 1 (T1). Starting from a prototype molecule—sunflower trypsin inhibitor-1 (SFTI-1)—we obtained light-controllable inhibitors of T1 with Ki in the low nanomolar range, whose activity could be modulated over 20-fold by irradiation. The inhibitory potency as well as resistance to proteolytic degradation were systematically studied on a series of 17 SFTI-1 analogues. The hydrogen bond network that stabilizes the structure of inhibitors and possibly the enzyme–inhibitor binding dynamics were affected by isomerization of the photoswitch. The feasibility of manipulating enzyme activity in time and space was demonstrated by controlled digestion of gelatin-based hydrogel and an antimicrobial peptide BP100-RW. Finally, our design principles of diarylethene photoswitches are shown to apply also for the development of other serine protease inhibitors


Verlagsausgabe §
DOI: 10.5445/IR/1000137495
Veröffentlicht am 21.09.2021
Originalveröffentlichung
DOI: 10.1002/anie.202108847
Scopus
Zitationen: 5
Web of Science
Zitationen: 4
Dimensions
Zitationen: 6
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische Grenzflächen (IBG)
Institut für Mikrostrukturtechnik (IMT)
Institut für Organische Chemie (IOC)
Publikationstyp Zeitschriftenaufsatz
Publikationsdatum 27.09.2021
Sprache Englisch
Identifikator ISSN: 1433-7851, 0570-0833, 1521-3773
KITopen-ID: 1000137495
HGF-Programm 47.14.01 (POF IV, LK 01) Molekular Information Processing in Cellular Systems
Erschienen in Angewandte Chemie - International Edition
Verlag John Wiley and Sons
Band 60
Heft 40
Seiten 21789-21794
Vorab online veröffentlicht am 16.07.2021
Nachgewiesen in Scopus
Dimensions
Web of Science
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