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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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Received: 30 December 2013; in revised form: 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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

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.


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