Cell-penetrating cis-gamma-amino-l-proline-derived peptides.
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.
Farrera-Sinfreu
Josep
J
Barcelona Biomedical Research Institute, Combinatorial Chemistry Unit, Barcelona Science Park, University of Barcelona, Spain.
Giralt
Ernest
E
Castel
Susanna
S
Albericio
Fernando
F
Royo
Miriam
M
D000409:Alanine / Q000737:chemistry; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004705:Endocytosis; D005434:Flow Cytometry; D015696:Gene Products, tat / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D007930:Leucine / Q000737:chemistry; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010447:Peptide Hydrolases / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism*; D010649:Phenylalanine / Q000737:chemistry; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry*; D013696:Temperature
D015696:Gene Products, tat; D010455:Peptides; D010649:Phenylalanine; D011392:Proline; D010447:Peptide Hydrolases; D007930:Leucine; D000409:Alanine