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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Novel Synthesis of Benzophenone Units forPhoto-Affinity LabelingShirly Naveh 1 , Carni Lipson 2 , Michal Breker 3 , Yftah Tal-Gan 1 ,Maya Schuldiner 3 , Michal Sharon 2 , and Chaim Gilon 11 Institute of Chemistry, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel;2 Department of Biological Chemistry, The Weizmann Institute of Science, 76100, Rehovot,Israel; 3 Department of Molecular Genetics, Weizmann Institute of Science,76100, Rehovot, IsraelIntroductionPeptides are a common tool for the study of protein-protein interactions. Benzophenone(BP) is an attractive photo-affinity label which covalently binds to the inactive C-H bondsof the protein, upon exposure to UV irradiation [1]. In order to use BP for the study ofprotein interactions, a peptide-BP conjugate must be synthesized. The addition of BP to thetarget molecule has often proven to be a difficult synthetic step. Here we describe a onepot, two step synthesis of BP units that are compatible with standard solid phase peptidesynthesis procedures. The proximity between the BP moiety and the peptidepharmacophores can affect both binding and activity, thus we developed BP units usingspacers of varying lengths. In addition, the spacer has a dominant effect on the site at whichthe BP binds to the protein, and the use of various lengths enables more complete mappingof the binding site.Results and DiscussionIn order to mainstream the use of BP, we have developed a one pot, two steps synthesis ofBP units suitable for standard solid phase peptide synthesis procedures. The synthesis isbased on coupling between the carboxy group of Boc-amino-alkylene carboxylic acid andthe amine of 2-amino-benzophenone, followed by Boc removal (Figure 1). Coupling wasperformed using phosgene as the coupling reagent. The product was treated with TFA toobtain the BP unit. Purification was performed on silica gel.Fig. 1. Synthesis of BP units.Fig. 2. Structure of SN1 containing photo-affinity label.156