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Molecules 2014, 19(2), 2481-2496; doi:10.3390/molecules19022481
Article

Pharmacophore Generation from a Drug-like Core Molecule Surrounded by a Library Peptide via the 10BASEd-T on Bacteriophage T7

1,†
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1,†
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2
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2
 and
1,*
1 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 2 Department of Chemistry and Bioscience, Graduate School of Science and Engineering, Kagoshima University, 1-21-35 Korimoto, Kagoshima, Kagoshima 890-0065, Japan These authors contributed equally and are considered as co-first authors.
* Author to whom correspondence should be addressed.
Received: 30 December 2013 / Revised: 10 February 2014 / Accepted: 12 February 2014 / Published: 21 February 2014
(This article belongs to the Special Issue Bioorthogonal Chemistry)
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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.
Keywords: 10BASEd-T; bacteriophage T7; chemical modification; drug-like molecule; peptide library; phage display; pharmacophore; salicylic acid; site-specific conjugation; thioether 10BASEd-T; bacteriophage T7; chemical modification; drug-like molecule; peptide library; phage display; pharmacophore; salicylic acid; site-specific conjugation; thioether
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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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.

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