ZFIN ID: ZDB-PUB-200125-6
Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos
Afonin, S., Babii, O., Reuter, A., Middel, V., Takamiya, M., Strähle, U., Komarov, I.V., Ulrich, A.S.
Date: 2020
Source: Beilstein journal of organic chemistry   16: 39-49 (Journal)
Registered Authors: Middel, Volker, Strähle, Uwe, Takamiya, Masanari
Keywords: diarylethene photoswitch, gramicidin S, membrane-active peptides, photopharmacology, zebrafish embryotoxicity model
MeSH Terms: none
PubMed: 31976015 Full text @ Beilstein J Org Chem
This study evaluates the embryotoxicity of dithienylethene-modified peptides upon photoswitching, using 19 analogues based on the β-hairpin scaffold of the natural membranolytic peptide gramicidin S. We established an in vivo assay in two variations (with ex vivo and in situ photoisomerization), using larvae of the model organism Danio rerio, and determined the toxicities of the peptides in terms of 50% lethal doses (LD50). This study allowed us to: (i) demonstrate the feasibility of evaluating peptide toxicity with D. rerio larvae at 3-4 days post fertilization, (ii) determine the phototherapeutic safety windows for all peptides, (iii) demonstrate photoswitching of the whole-body toxicity for the dithienylethene-modified peptides in vivo, (iv) re-analyze previous structure-toxicity relationship data, and (v) select promising candidates for potential clinical development.