Pharmacophore generation from a drug-like core molecule surrounded by a library peptide via the 10BASEd-T on bacteriophage T7

Molecules. 2014 Feb 21;19(2):2481-96. doi: 10.3390/molecules19022481.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / chemistry*
  • Amino Acid Sequence
  • Bacteriophage T7 / chemistry*
  • Drug Compounding
  • Humans
  • Hydrocarbons, Halogenated / chemistry*
  • Peptide Library*
  • Peptides / chemistry*
  • Protein Processing, Post-Translational
  • Salicylic Acid / chemistry
  • Streptavidin / chemistry


  • Acetamides
  • Hydrocarbons, Halogenated
  • Peptide Library
  • Peptides
  • Streptavidin
  • Salicylic Acid