Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos
| Autor: | Volker Middel, Igor V. Komarov, Masanari Takamiya, Sergii Afonin, Aline Reuter, Anne S. Ulrich, Uwe Strähle, Oleg Babii |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Life sciences
biology Danio Peptide Gramicidin S 010402 general chemistry 01 natural sciences Full Research Paper lcsh:QD241-441 chemistry.chemical_compound gramicidin s lcsh:Organic chemistry In vivo ddc:570 photopharmacology lcsh:Science chemistry.chemical_classification 010405 organic chemistry Organic Chemistry biology.organism_classification diarylethene photoswitch Cyclic peptide 0104 chemical sciences 3. Good health Chemistry Biochemistry chemistry Toxicity Gramicidin zebrafish embryotoxicity model lcsh:Q membrane-active peptides Ex vivo |
| Zdroj: | Beilstein Journal of Organic Chemistry Beilstein journal of organic chemistry, 16, 39–49 Beilstein Journal of Organic Chemistry, Vol 16, Iss 1, Pp 39-49 (2020) |
| ISSN: | 1860-5397 |
| DOI: | 10.3762/bjoc.16.6 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|