Modulation of the Peptide Backbone Conformation by the Selenoxo Photoswitch

摘要

The conformation of the polypeptide backbone plays an importantnrole in determining protein structure, stability, and dynamics.n1nExternal control of conformational changes in a backbone as definednby photoswitching at the one-bond level would provide a soundnbasis for structure function studies of proteins. Therefore, incor-nporation of a photoresponsive element into the backbone, to controlnstructure and bioactivity by a soft light switch, is of great interest.nHerein, for the purpose of obtaining more stable peptide bondnconformers characterized by a bathochromic shift of the π π* bandnrelative to the oxo or thioxo peptide UV/vis absorption, wenintroduced a single selenoxo peptide bond into the peptidenbackbone. Principally, the UV/vis spectral properties of amidesnallow us to trigger the cis/trans peptide bond photoswitch.n2nHowever, the repetitive character of the peptide bond in proteinsnand the low excitation wavelength of ∼200 nm required fornproducing excess cis isomer in the photostationary state (PSS) wouldnconsiderably hamper the interpretation of photoisomerizationnexperiments in oligopeptides and proteins. Azobenzene as anbackbone constituent, for instance, was shown to trigger the foldingnand unfolding of -helix and u0002-hairpin model peptides on thenfemtosecond time scale.n3nIt should be noted, however, that thenazobenzene moiety interrupts the regularly repeating pattern of anpolypeptide chain, underlining the need for a chemically lessnperturbing backbone substitution.