title: Photo-control of peptide conformation on a timescale of seconds with a conformationally constrained, blue-absorbing, photo-switchable linker.
abstract: Azobenzene derivatives can be used to reversibly photo-regulate conformation and activity when introduced as intramolecular bridges in peptides and proteins. Here we report the design, synthesis, and characterization of an azobenzene derivative that absorbs between 400-450 nm in aqueous solution to produce the cis isomer, and relaxes back to the trans isomer with a half-life of a few seconds at room temperature. In the trans form, the linker can span a distance of approximately 25 A, so that it can bridge Cys residues spaced i, i + 15 in an alpha-helix. Switching of the azobenzene cross-linker from trans to cis causes a decrease in the helix content of peptides where the linker is attached via Cys residues spaced at i, i + 15 and i, i + 14 positions, no change in helix content with Cys residues spaced i, i + 11 and an increase in helix content in a peptide with Cys residues spaced at i, i + 7. In the presence of 10 mM reduced glutathione, the azobenzene cross-linker continued to photo-switch after 24 hours. This cross-linker design thus expands the possibilities for fast photo-control of peptide and protein structure in biochemical systems.
authors.affiliation: Department of Chemistry, University of Toronto, 80 St. George St.. Toronto, ON M5S 3H6, Canada.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Beharry
authors.forename: Oleg
authors.initials: O
authors.lastname: Sadovski
authors.forename: G Andrew
authors.initials: GA
authors.lastname: Woolley
mesh_terms: D000042:Absorption; D000595:Amino Acid Sequence; D001391:Azo Compounds / Q000737:chemistry; D003116:Color; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D015195:Drug Design; D005978:Glutathione / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007536:Isomerism; D007700:Kinetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D010777:Photochemistry; D011487:Protein Conformation / Q000187:drug effects; D012997:Solvents / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013696:Temperature; D013997:Time Factors
chemical_list: D001391:Azo Compounds; D003432:Cross-Linking Reagents; D010455:Peptides; D012997:Solvents; D013438:Sulfhydryl Compounds; C009850:azobenzene; D005978:Glutathione