Cell-Penetrating <i>cis</i>-γ-Amino-<scp>l</scp>-Proline-Derived Peptides

Abstract

The synthesis of cis-gamma-amino-l-proline oligomers functionalized at the proline alpha-amine with several groups that mimic the side chains of natural amino acids, including alanine, leucine, and phenylalanine, is herein described. These gamma-peptides enter into different cell lines (COS-1 and HeLa) via an endocytic mechanism. The ability of these compounds to be taken up into cells was studied at 37 degrees C and 4 degrees C by plate fluorimetry, flow cytometry, and confocal microscopy. In addition to their capacity for cellular uptake, these unnatural short length oligomers offer advantages over the well-known penetrating TAT peptide, such as being less toxic than TAT and protease resistance.