Cationic oligonucleotide-peptide conjugates with aggregating properties enter efficiently into cells while maintaining hybridization properties and enzymatic recognition.
Oligonucleotide delivery is a crucial issue for therapeutical purposes and is often addressed by conjugation to short cationic peptides although with controversial results. To further examine this mechanism, a 15-mer anionic oligonucleotide was conjugated to a cationic peptide in order to obtain a diblock compound with an overall positive charge with aggregation properties. These microaggregates were efficiently internalized in cells via the expeditious pathway used by commercial gene delivery systems. Moreover, stability of the duplex formed with the complementary sequence increased without inhibiting oligonucleotide enzyme recognition as shown by the properties of the conjugate to prime chain elongation by Taq DNA polymerase in a linear amplification/sequencing process.
Fraley
Andrew W
AW
Université Louis Pasteur de Strasbourg, Laboratoire de Chimie Génétique associé au CNRS, Faculté de Pharmacie, BP 60024, 67401 Illkirch, France.
Pons
Bénédicte
B
Dalkara
Deniz
D
Nullans
Gérard
G
Behr
Jean-Paul
JP
Zuber
Guy
G
D000595:Amino Acid Sequence; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation
D009841:Oligonucleotides; D010455:Peptides