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

Molecules

Yuuki Tokunaga¹  Yuuki Azetsu¹  Keisuke Fukunaga¹  Takaaki Hatanaka²  Yuji Ito² 

[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; E-Mails:;Department of Chemistry and Bioscience, Graduate School of Science and Engineering, Kagoshima University, 1-21-35 Korimoto, Kagoshima, Kagoshima 890-0065, Japan; E-Mails:

关键词: 10BASE_d-T;    bacteriophage T7;    chemical modification;    drug-like molecule;    peptide library;    phage display;    pharmacophore;    salicylic acid;    site-specific conjugation;    thioether;   

DOI  :  10.3390/molecules19022481

来源: mdpi

【 摘 要 】

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 (10BASE_d-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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.