Journal article
Discovery of metabolically stabilized electronegative polyacridine-PEG peptide DNA open polyplexes
Bioconjugate chemistry, Vol.21(4), pp.723-730
04/21/2010
DOI: 10.1021/bc900514s
PMCID: PMC2860281
PMID: 20218669
Abstract
Cationic condensing peptides and polymers bind electrostatically to DNA to form cationic polyplexes. While many cationic polyplexes are able to achieve in vitro transfection mediated through electrostatic interactions, few have been able to mediate gene transfer in vivo. The present study describes the development and testing of polyacridine PEG-peptides that bind to plasmid DNA by intercalation resulting in electronegative open polyplex DNA. Polyacridine PEG-peptides were prepared by chemically conjugating 6-(9-acridinylamino) hexanoic acid onto side chains of Lys in PEG-Cys-Trp-(Lys)(3, 4, or 5). The resulting PEG-Cys-Trp-(Lys-(Acr))(3, 4, or 5) peptides bound tightly to DNA by polyintercalation, rather than electrostatic binding. Unlike polycationic polyplexes, polyacridine PEG-peptide polyplexes were anionic and open coiled, as revealed by zeta potential and atomic force microscopy. PEG-Cys-Trp-(Lys-(Acr))(5) showed the highest DNA binding affinity and the greatest ability to protect DNA from metabolism by DNase. Polyacridine PEG-peptide DNA open polyplexes were dosed intramuscularly and electroporated in mice to demonstrate their functional activity in gene transfer. These results establish polyacridine PEG-peptide DNA open polyplexes as a novel gene delivery method for in vivo use.
Details
- Title: Subtitle
- Discovery of metabolically stabilized electronegative polyacridine-PEG peptide DNA open polyplexes
- Creators
- Christian A Fernandez - Divisions of Pharmaceutics and Medicinal & Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, USANicholas J BaumhoverKevin AndersonKevin G Rice
- Resource Type
- Journal article
- Publication Details
- Bioconjugate chemistry, Vol.21(4), pp.723-730
- DOI
- 10.1021/bc900514s
- PMID
- 20218669
- PMCID
- PMC2860281
- NLM abbreviation
- Bioconjug Chem
- ISSN
- 1043-1802
- eISSN
- 1520-4812
- Publisher
- United States
- Grant note
- DK066212 / NIDDK NIH HHS T32 GM067795 / NIGMS NIH HHS R01 DK066212 / NIDDK NIH HHS R01 DK066212-04 / NIDDK NIH HHS R01 GM087653 / NIGMS NIH HHS
- Language
- English
- Date published
- 04/21/2010
- Academic Unit
- Radiology; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984065694702771
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