Poster Presentation 10th Australian Peptide Conference 2013

Here, we report that site-specific introduction of haloacetamide derivatives into designated cysteines on a displaying peptide at a capsid protein (gp10) of a bacteriophage T7 has been achieved. This easiest gp10-based thioetherification (10BASE_d-T) undergoes almost quantitatively in one-pot without side reaction or loss of phage infectivity. Construction of such peptide-based library possessing  non-natural structure will be useful for future drug discovery. For this aim, we constructed a tetramethylrhodamine-conjugated peptide library and isolated a glutathione S-tarnsferase binder with a dissociation constant of 3.6μM. Furthermore, we successfully constructed stapled peptide libraries. Affinity selection against target proteins with the peptide library is currently underway, and we have already obtained several candidates. Functional analysis of the peptides in vitro and in vivo is also in progress.

In conclusion, we established a general and instant method of post-translational chemical modification for peptide library on T7 phage.