An improved large-scale synthesis of PEG-peptides for gene delivery.
Polyethylene glycol (PEG)-peptides are under development as components of nonviral gene delivery systems. Several earlier reports have demonstrated that covalent attachment of PEG to the surface of peptide condensed DNA particles blocks non-specific biodistribution during gene targeting. In this study, we report an improved large-scale synthesis and purification of a DNA condensing PEG-peptide used for gene delivery. The new method takes advantage of low-pressure cation-exchange chromatography to isolate dimeric Cys-Trp-Lys(18). The dimeric peptide was reduced and directly conjugated with PEG-maleimide resulting in PEG-Cys-Trp-Lys(18). The PEG-peptide was purified by low-pressure chromatography affording 50 mumol (400 mg) quantities of PEG-peptide in >95% purity. The approach offers the advantage of avoiding preparative high-performance liquid chromatography (HPLC) purifications of polylysine peptides to increase yield and capacity.
Chen
C-P
CP
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa, 115 South Grand Avenue, Iowa City, IA 52242, USA.
Park
Y
Y
Rice
K G
KG
D019281:Dimerization; D018014:Gene Transfer Techniques; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011107:Polylysine
D010455:Peptides; D011107:Polylysine; D011092:Polyethylene Glycols