Journal article
Synthesis and In Vitro Testing of New Potent Polyacridine−Melittin Gene Delivery Peptides
Bioconjugate chemistry, Vol.21(1), pp.74-83
01/20/2010
DOI: 10.1021/bc9003124
PMCID: PMC2813064
PMID: 19968269
Abstract
The combination of a polyacridine peptide modified with a melittin fusogenic peptide results in a potent gene transfer agent. Polyacridine peptides of the general formula (Acr-X) n -Cys were prepared by solid-phase peptide synthesis, where Acr is Lys modified on its ε-amine with acridine, X is Arg, Leu, or Lys and n is 2, 3, or 4 repeats. The Cys residue was modified by either a maleimide−melittin or a thiolpyridine-Cys-melittin fusogenic peptide resulting in reducible or non-reducible polyacridine−melittin peptides. Hemolysis assays established that polyacridine−melittin peptides retained their membrane lytic potency relative to melittin at pH 7.4 and 5. When combined with plasmid DNA, the membrane lytic potency of polyacridine−melittin peptides was neutralized. Gene transfer experiments in multiple cell lines established that polyacridine−melittin peptides mediate expression as efficiently as PEI. The expression was very dependent upon a disulfide bond linking polyacridine to melittin. The gene transfer was most efficient when X is Arg and n is 3 or 4 repeats. These studies establish polyacridine peptides as a novel DNA binding anchor peptide.
Details
- Title: Subtitle
- Synthesis and In Vitro Testing of New Potent Polyacridine−Melittin Gene Delivery Peptides
- Creators
- Nicholas J BaumhoverKevin AndersonChristian A FernandezKevin G Rice
- Resource Type
- Journal article
- Publication Details
- Bioconjugate chemistry, Vol.21(1), pp.74-83
- DOI
- 10.1021/bc9003124
- PMID
- 19968269
- PMCID
- PMC2813064
- NLM abbreviation
- Bioconjug Chem
- ISSN
- 1043-1802
- eISSN
- 1520-4812
- Publisher
- American Chemical Society
- Alternative title
- Polyacridine−Melittin Gene Delivery Peptides
- Language
- English
- Date published
- 01/20/2010
- Academic Unit
- Radiology; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984065690002771
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