Diarylethene-Based Photoswitchable Inhibitors of Serine Proteases

被引：20

作者：

Babii, Oleg ^{[1
,2
]}

Afonin, Sergii ^{[1
]}

Diel, Christian ^{[3
]}

Huhn, Marcel ^{[3
]}

Dommermuth, Jennifer ^{[3
]}

Schober, Tim ^{[3
,5
]}

Koniev, Serhii ^{[4
]}

Hrebonkin, Andrii ^{[1
]}

Nesterov-Mueller, Alexander ^{[2
]}

Komarov, Igor V. ^{[4
,5
]}

Ulrich, Anne S. ^{[1
,3
]}

机构：

[1] Karlsruhe Inst Technol KIT, Inst Biol Interfaces IBG 2, POB 3640, D-76021 Karlsruhe, Germany

[2] KIT, Inst Microstruct Technol IMT, Hermann von Helmholtz Pl 1, D-76344 Eggenstein Leopoldshafen, Germany

[3] KIT, Inst Organ Chem IOC, Fritz Haber Weg 6, D-76131 Karlsruhe, Germany

[4] Taras Shevchenko Natl Univ Kyiv, Vul Volodymyrska 60, UA-1601 Kiev, Ukraine

[5] Lumobiot GmbH, Auer Str 2, D-76227 Karlsruhe, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2021年 / 60卷 / 40期

关键词：

bicyclic peptide; diarylethene photoswitch; hydrogel photoregulation; serine protease inhibitors; trypsin; EXCHANGE-MASS-SPECTROMETRY; TRYPSIN-INHIBITOR; PROTEINASE-INHIBITOR; POTENT INHIBITORS; SMART MATERIALS; PEPTIDE; DESIGN; SFTI-1; MATRIPTASE; H-1-NMR;

D O I：

10.1002/anie.202108847

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 K-i 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.

引用

页码：21789 / 21794

页数：6

共 71 条

[71] The Endeavor of Diarylethenes: New Structures, High Performance, and Bright Future [J].

Zhang, Junji ;

Tian, He .

ADVANCED OPTICAL MATERIALS, 2018, 6 (06)

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