Mapping the Azolog Space Enables the Optical Control of New Biological Targets

Morstein, Johannes; Awale, Mahendra; Reymond, Jean-Louis; Trauner, Dirk (2019). Mapping the Azolog Space Enables the Optical Control of New Biological Targets. ACS central science, 5(4), pp. 607-618. ACS Publications 10.1021/acscentsci.8b00881

[img]
Preview
Text
acscentsci.8b00881.pdf - Published Version
Available under License Publisher holds Copyright.

Download (4MB) | Preview

Photopharmacology relies on molecules that change their biological activity upon irradiation. Many of these are derived from known drugs by replacing their core with an isosteric azobenzene photoswitch (azologization). The question is how many of the known bioactive ligands could be addressed in such a way. Here, we systematically assess the space of molecules amenable to azologization from databases of bioactive molecules (DrugBank, PDB, CHEMBL) and the Cambridge Structural Database. Shape similarity scoring functions (3DAPfp) and analyses of dihedral angles are employed to quantify the structural homology between a bioactive molecule and the cis or trans isomer of its corresponding azolog (“azoster”) and assess which isomer is likely to be active. Our analysis suggests that a very large number of bioactive ligands (>40 000) is amenable to azologization and that many new biological targets could be addressed with photopharmacology. N-Aryl benzamides, 1,2-diarylethanes, and benzyl phenyl ethers are particularly suited for this approach, while benzylanilines and sulfonamides appear to be less well-matched. On the basis of our analysis, the majority of azosters are expected to be active in their trans form. The broad applicability of our approach is demonstrated with photoswitches that target a nuclear hormone receptor (RAR) and a lipid processing enzyme (LTA4 hydrolase).

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Awale, Mahendra and Reymond, Jean-Louis

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

2374-7943

Publisher:

ACS Publications

Language:

English

Submitter:

Sandra Tanja Zbinden Di Biase

Date Deposited:

21 Jan 2020 15:48

Last Modified:

21 Jan 2020 15:48

Publisher DOI:

10.1021/acscentsci.8b00881

BORIS DOI:

10.7892/boris.138453

URI:

https://boris.unibe.ch/id/eprint/138453

Actions (login required)

Edit item Edit item
Provide Feedback