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.
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Tokunaga, Y.; Azetsu, Y.; Fukunaga, K.; Hatanaka, T.; Ito, Y.; Taki, M. Pharmacophore Generation from a Drug-like Core Molecule Surrounded by a Library Peptide via the 10BASEd-T on Bacteriophage T7. Molecules 2014, 19, 2481-2496.
Tokunaga Y, Azetsu Y, Fukunaga K, Hatanaka T, Ito Y, Taki M. Pharmacophore Generation from a Drug-like Core Molecule Surrounded by a Library Peptide via the 10BASEd-T on Bacteriophage T7. Molecules. 2014; 19(2):2481-2496.
Tokunaga, Yuuki; Azetsu, Yuuki; Fukunaga, Keisuke; Hatanaka, Takaaki; Ito, Yuji; Taki, Masumi. 2014. "Pharmacophore Generation from a Drug-like Core Molecule Surrounded by a Library Peptide via the 10BASEd-T on Bacteriophage T7." Molecules 19, no. 2: 2481-2496.