title: The effect of azobenzene cross-linker position on the degree of helical peptide photo-control.
abstract: Photo-switchable α-helical peptides offer a valuable tool to probe protein-biomacromolecule interactions in a spatiotemporally controlled manner. We synthesized a series of 32 residue peptides (AA32 s) with the core structure Ac-W-(E1A2A3A4R5)6-Q-NH2 and introduced the azobenzene based cross-linker BSBCA via reaction with Cys residues spaced at i, i + 7 intervals in different positions along the helix. UV/Vis measurements show that the composition of the photostationary state as well as thermal relaxation rates do not change considerably with changes in cross-linker position. CD analysis shows that photo-control of helix folding/unfolding is most effective when the cross-linker is targeted to the middle of the peptide so long as this segment has a high intrinsic helical propensity. The largest degree of photo-controlled conformational change occurred when a cross-linked central region of high intrinsic helicity was followed on the C-terminal side by a region of lower intrinsic helicity. This indicates the BSBCA cross-linker can act as a nucleation site for N-to-C propagation of a helix. These data help to guide the choice of cross-linking site in larger peptides and proteins where photo-control of conformation is desired.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Ali
authors.forename: G Andrew
authors.initials: GA
authors.lastname: Woolley
mesh_terms: D000595:Amino Acid Sequence; D001391:Azo Compounds / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013425:Sulfanilic Acids / Q000737:chemistry*
chemical_list: C575877:3,3'-bis(sulfonato)-4,4'-bis(chloroacetamide)azobenzene; D001391:Azo Compounds; D003432:Cross-Linking Reagents; D010455:Peptides; D013425:Sulfanilic Acids; C009850:azobenzene