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Issue 14, 2020
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Visible-light-driven photocontrol of the Trp-cage protein fold by a diazocine cross-linker

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Abstract

Diazocines are characterized by extraordinary photochemical properties rendering them of particular interest for switching the conformation of biomolecules with visible light. Current developments afford synthetic access to unprecedented diazocine derivatives promising particular opportunities in photocontrol of proteins and biological systems. In this work, the well-established approach of photocontrolling the secondary structure of α-helices was exploited using a diazocine to reversibly fold and unfold the tertiary structure of a small protein. The protein of choice was the globulary folded Trp-cage, a widely used model system for the elucidation of protein folding pathways. A specifically designed, short and rigid dicarboxy-functionalized diazocine-based cross-linker was attached to two solvent-exposed side chains at the α-helix of the miniprotein through the use of a primary amine-selective active ester. This cross-linking strategy is orthogonal to the common cysteine-based chemistry. The cross-linked Trp-cage was successfully photoisomerized and exhibited a strong correlation between protein fold and diazocine isomeric state. As determined by NMR spectroscopy, the cis-isomer stabilized the fold, while the trans-isomer led to complete protein unfolding. The successful switching of the protein fold in principle demonstrates the ability to control protein function, as the activity depends on their structural integrity.

Graphical abstract: Visible-light-driven photocontrol of the Trp-cage protein fold by a diazocine cross-linker

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Supplementary files

Article information


Submitted
12 Nov 2019
Accepted
19 Dec 2019
First published
24 Mar 2020

This article is Open Access

Org. Biomol. Chem., 2020,18, 2650-2660
Article type
Paper

Visible-light-driven photocontrol of the Trp-cage protein fold by a diazocine cross-linker

N. Preußke, W. Moormann, K. Bamberg, M. Lipfert, R. Herges and F. D. Sönnichsen, Org. Biomol. Chem., 2020, 18, 2650
DOI: 10.1039/C9OB02442E

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    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
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    [Original citation] - Published by The Royal Society of Chemistry.

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