An improved large-scale synthesis of PEG-peptides for gene delivery

被引:4
作者
Chen, CP [1 ]
Park, Y [1 ]
Rice, KG [1 ]
机构
[1] Univ Iowa, Coll Pharm, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA
来源
JOURNAL OF PEPTIDE RESEARCH | 2004年 / 64卷 / 06期
关键词
conjugation; deoxyribonucleic acid condensate; gene delivery; polyethylene glycol; polylysine;
D O I
10.1111/j.1399-3011.2004.00195.x
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:237 / 243
页数:7
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