Design and Application of a DNA-Encoded Macrocyclic Peptide Library

ACS Chem Biol. 2018 Jan 19;13(1):53-59. doi: 10.1021/acschembio.7b00852. Epub 2017 Dec 4.

Abstract

A DNA-encoded macrocyclic peptide library was designed and synthesized with 2.4 × 1012 members composed of 4-20 natural and non-natural amino acids. Affinity-based selection was performed against two therapeutic targets, VHL and RSV N protein. On the basis of selection data, some peptides were selected for resynthesis without a DNA tag, and their activity was confirmed.

MeSH terms

  • Amino Acids / chemistry
  • DNA / chemistry
  • Drug Evaluation, Preclinical / methods
  • Molecular Targeted Therapy
  • Peptide Library*
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / genetics
  • Peptides, Cyclic / pharmacology*
  • Polymerase Chain Reaction
  • Respiratory Syncytial Viruses
  • Viral Proteins / antagonists & inhibitors
  • Viral Proteins / chemistry
  • Viral Proteins / metabolism*
  • Von Hippel-Lindau Tumor Suppressor Protein / chemistry
  • Von Hippel-Lindau Tumor Suppressor Protein / metabolism*

Substances

  • Amino Acids
  • Peptide Library
  • Peptides, Cyclic
  • Viral Proteins
  • DNA
  • Von Hippel-Lindau Tumor Suppressor Protein
  • VHL protein, human