title: Pharmacophore generation from a drug-like core molecule surrounded by a library peptide via the 10BASEd-T on bacteriophage T7.
abstract: We have achieved site-specific conjugation of several haloacetamide derivatives into designated cysteines on bacteriophage T7-displayed peptides, which are fused to T7 capsid protein gp10. This easiest gp10 based-thioetherification (10BASEd-T) undergoes almost quantitatively like a click reaction without side reaction or loss of phage infectivity. The post-translational modification yield, as well as the site-specificity, is quantitatively analyzed by a fluorescent densitometric analysis after gel electrophoresis. The detailed structure of the modified peptide on phage is identified with tandem mass spectrometry. Construction of such a peptide-fused phage library possessing non-natural core structures will be useful for future drug discovery. For this aim, we propose a novel concept of pharmacophore generation from a drug-like molecule (i.e., salicylic acid) conjugated with surrounding randomized peptides. By using the hybrid library, streptavidin-specific binders are isolated through four rounds of biopanning.
authors.affiliation: Department of Engineering Science, Bioscience and Technology Program, The Graduate School of Informatics and Engineering, The University of Electro-Communications (UEC), 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan. t1333065@edu.cc.uec.ac.jp.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Tokunaga
authors.affiliation: Department of Engineering Science, Bioscience and Technology Program, The Graduate School of Informatics and Engineering, The University of Electro-Communications (UEC), 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan. a1013005@edu.cc.uec.ac.jp.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Azetsu
authors.affiliation: Department of Engineering Science, Bioscience and Technology Program, The Graduate School of Informatics and Engineering, The University of Electro-Communications (UEC), 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan. fukunaga-ks@pc.uec.ac.jp.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Fukunaga
authors.affiliation: Department of Chemistry and Bioscience, Graduate School of Science and Engineering, Kagoshima University, 1-21-35 Korimoto, Kagoshima, Kagoshima 890-0065, Japan. k7808291@kadai.jp.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hatanaka
authors.affiliation: Department of Chemistry and Bioscience, Graduate School of Science and Engineering, Kagoshima University, 1-21-35 Korimoto, Kagoshima, Kagoshima 890-0065, Japan. k2174603@kadai.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Engineering Science, Bioscience and Technology Program, The Graduate School of Informatics and Engineering, The University of Electro-Communications (UEC), 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan. taki@pc.uec.ac.jp.
authors.forename: Masumi
authors.initials: M
authors.lastname: Taki
mesh_terms: D000081:Acetamides / Q000737:chemistry*; D000595:Amino Acid Sequence; D017123:Bacteriophage T7 / Q000737:chemistry*; D004339:Drug Compounding; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000737:chemistry*; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry*; D011499:Protein Processing, Post-Translational; D020156:Salicylic Acid / Q000737:chemistry; D019809:Streptavidin / Q000737:chemistry
chemical_list: D000081:Acetamides; D006846:Hydrocarbons, Halogenated; D019151:Peptide Library; D010455:Peptides; D019809:Streptavidin; D020156:Salicylic Acid