Quantitative Comparison of the Relative Cell Permeability of Cyclic and Linear Peptides

SummaryCyclic peptides are of considerable interest as potential protein ligands. It has been postulated that cyclic molecules might be more cell permeable than their linear counterparts due to their reduced conformational flexibility. We report a study that tests this hypothesis by using a quantitative, reporter gene-based assay that measures the relative cell permeability of steroid conjugates of molecules of interest. We demonstrate that cyclic peptides are, in fact, not generally more permeable than their linear counterparts.