High-throughput evaluation of relative cell permeability between peptoids and peptides.
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.
Tan
Niclas C
NC
Division of Translational Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Yu
Peng
P
Kwon
Yong-Uk
YU
Kodadek
Thomas
T
D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006367:HeLa Cells; D006801:Humans; D006860:Hydrogen Bonding; D007536:Isomerism; D049449:Luminescence; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000502:physiology*; D034444:Peptoids / Q000737:chemistry* / Q000502:physiology*; D048790:Renilla
D019151:Peptide Library; D010455:Peptides; D034444:Peptoids