Journal of the American Chemical Society
Journal of the American Chemical Society
5 years ago

Adhesive Photoswitch: Selective Photochemical Modulation of Enzymes under Physiological Conditions

Adhesive Photoswitch: Selective Photochemical Modulation of Enzymes under Physiological Conditions
Rina Mogaki, Takuzo Aida, Kou Okuro
We developed a water-soluble adhesive photoswitch (Gluen-Azo-SA, average n = 5) that selectively binds to a target enzyme and photochemically modulates its enzymatic activity even in cell lysates. Its design strategy features a photochromic azobenzene unit (Azo), which carries on one side an inhibitory motif for the target enzyme and on the other a glue part (Gluen) that utilizes its multiple guanidinium ion (Gu+) pendants for adhering onto the target surface. The target of Gluen-Azo-SA is carbonic anhydrase (CA) because sulfonamide (SA) derivatives, such as SA at the terminus of Gluen-Azo-SA, are known to bind selectively to the CA active site. The SA moiety, upon docking at the CA active site, possibly guides the connecting Gluen part to an oxyanion-rich area in proximity to the active site for adhesion, so that the conjugation between Gluen-Azo-SA and CA is ensured. With this geometry, the photochemical isomerization of the Azo unit likely generates a push–pull motion of SA, resulting in its docking and undocking at the active site of CA with the help of a competing substrate. Consequently, Gluen-Azo-SA can selectively photomodulate the enzymatic action of CA even in cell lysates. Azo-SA without Gluen can likewise suppress the enzymatic activity of CA by docking SA at its active site, but the resulting CA/Azo-SA conjugate, in contrast, does not respond to light.

Publisher URL: http://dx.doi.org/10.1021/jacs.7b05151

DOI: 10.1021/jacs.7b05151

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.