Synthesis of sulfhydryl cross-linking poly(ethylene glycol)-peptides and glycopeptides as carriers for gene delivery.
Sulfhydryl cross-linking poly(ethylene glycol) (PEG)-peptides and glycopeptides were prepared and tested for spontaneous polymerization by disulfide bond formation when bound to plasmid DNA, resulting in stable PEG-peptide and glycopeptide DNA condensates. A 20 amino acid synthetic peptide possessing a single sulfhydryl group on the N-terminal cysteine, with two or five internal acetamidomethyl (Acm)-protected cysteine residues, was reacted with either PEG vinyl sulfone or iodoacetamide tyrosinamide triantennary N-glycan. Following RP-HPLC purification, Acm groups were removed by silver tetrafluoroborate to generate sulfhydryl cross-linking PEG-peptides and glycopeptide that were characterized by either (1)H NMR or LC-MS. Sulfhydryl cross-linking PEG-peptides and glycopeptides were found to bind to plasmid DNA and undergo disulfide cross-linking resulting in stable DNA condensates with potential utility for in vivo gene delivery.
Park
Youmie
Y
College of Pharmacy, 428 Church Street, University of Michigan, Ann Arbor, Michigan 48109-1065, USA.
Kwok
Kai Y
KY
Boukarim
Chawki
C
Rice
Kevin G
KG
D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000138:chemical synthesis* / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006023:Glycoproteins / Q000138:chemical synthesis* / Q000737:chemistry; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*
D003432:Cross-Linking Reagents; D004220:Disulfides; D006023:Glycoproteins; D010455:Peptides; D011092:Polyethylene Glycols; D004247:DNA