Carboncarbon bond ligation between β-cyclodextrin and peptide by photo-irradiation

The formation of a stable covalent bond between β-cyclodextrin and different diphenyl-ketones (para-benzoylphenylalanine (pBz)Phe, para-benzoylbenzoic acid, pBzBz, and ketoprofen, KPF, under photo-irradiation is reported. These photo-probes have been incorporated into five peptides PEP1=Ac-Arg-Lys-Asp-Val-(pBz)Phe-NH2; PEP2=Ac-Arg-Lys-Val-(pBz)Phe-NH2; PEP3=Arg-Pro-(KPF)Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2; PEP4=N-(KPF)Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2; PEP5=Biot(O2)-Apa-Arg-Arg-Pro-(pBzBz)Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met(O2)-NH2. The carboncarbon ligation occurs both in solution and in solid state and whatever the position of the diphenyl ketone, the ketyl radical is able to recombinate with β-cyclodextrin radical even in solid state. Photochemistry of diphenylketone is a complementary and orthogonal approach to chemical modifications of primary hydroxyl functions of β-cyclodextrin.