Spiropyran‐Based Photoisomerizable α‐Amino Acid for Membrane‐Active Peptide Modification

• Published in: Chemistry : a European journal 2024-04, Vol.30 (22), p.e202400066-n/a
• Main Authors: Hrebonkin, Andrii, Afonin, Sergii, Nikitjuka, Anna, Borysov, Oleksandr V., Leitis, Gundars, Babii, Oleg, Koniev, Serhii, Lorig, Theo, Grage, Stephan L., Nick, Peter, Ulrich, Anne S., Jirgensons, Aigars, Komarov, Igor V.
• Format: Article
• Language: English
• Subjects: Actin; Amino acids; Azo compounds; Biocompatibility; BP100; Drug development; E coli; membrane-active peptides; Membranes; molecular photoswitches; Peptides; photopharmacology; Propionic acid; spiropyran; Spiropyrans; Toxicity
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202400066

Photoisomerizable peptides are promising drug candidates in photopharmacology. While azobenzene‐ and diarylethene‐containing photoisomerizable peptides have already demonstrated their potential in this regard, reports on the use of spiropyrans to photoregulate bioactive peptides are still scarce. This work focuses on the design and synthesis of a spiropyran‐derived amino acid, (S)‐2‐amino‐3‐(6'‐methoxy‐1',3',3'‐trimethylspiro‐[2H‐1‐benzopyran‐2,2'‐indolin‐6‐yl])propanoic acid, which is suitable for the preparation of photoisomerizable peptides. The utility of this amino acid is demonstrated by incorporating it into the backbone of BP100, a known membrane‐active peptide, and by examining the photoregulation of the membrane perturbation by the spiropyran‐containing peptides. The toxicity of the peptides (against the plant cell line BY‐2), their bacteriotoxicity (E. coli), and actin–auxin oscillator modulation ability were shown to be significantly dependent on the photoisomeric state of the spiropyran unit. A spiropyran‐derived α‐amino acid was carefully designed for the synthesis of photocontrollable bioactive peptides. Dramatic changes in structure and polarity occurring upon light exposure or dark adaptation of the spiropyran side chain can cause changes in the behavior of peptides in lipid membranes and living cells, as demonstrated on spiropyran‐containing analogs of the membrane‐active peptide BP100 (KKLFKKILKYL‐NH2).