High-throughput evaluation of relative cell permeability between peptoids and peptides

Niclas C. Tan, Peng Yu, Yong Uk Kwon, Thomas Kodadek

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

Peptides are limited in their use as drugs due to low cell permeability and vulnerability to proteases. In contrast, peptoids are immune to enzymatic degradation and some peptoids have been shown to be relatively cell permeable. In order to facilitate future design of peptoid libraries for screening experiments, it would be useful to have a high-throughput method to estimate the cell permeability of peptoids containing different residues. In this paper, we report the strengths and limitations of a high-throughput cell-based permeability assay that registers the relative ability of steroid-conjugated peptides and peptoids to enter a cell. A comparative investigation of the physicochemical properties and side chain composition of peptoids and peptides is described to explain the observed higher cell permeability of peptoids over peptides. These data suggest that the conversion of the monomeric residues in peptides to an N-alkylglycine moiety in peptoids reduced the hydrogen-bonding potential of the molecules and is the main contributor to the observed permeability improvement.

Original languageEnglish
Pages (from-to)5853-5861
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number11
DOIs
StatePublished - 1 Jun 2008

Keywords

  • Cell permeability
  • Cell-based assay
  • High-throughput assay
  • High-throughput cell permeability assay
  • Peptide
  • Peptidomimetics
  • Peptoid
  • Physicochemical properties
  • Solid-phase synthesis combinatorial library

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