Drug Discov Ther. 2014;8(4):165-172. (DOI: 10.5582/ddt.2014.01029)

Design of amphiphilic oligopeptides as models for fine tuning peptide assembly with plasmid DNA.

Goparaju GN, Gupta PK


We discuss the design of novel amphiphilic oligopeptides with hydrophobic and cationic amino acids to serve as models to understand peptide-DNA assembly. Biophysical and thermodynamic characterization of interaction of these amphiphilic peptides with plasmid DNA is presented. Peptides with at least +4 charges favor stable complex formation. Surface potential is dependent on the type of hydrophobic amino acid for a certain charge. Thermodynamically it is a spontaneous interaction between most of the peptides and plasmid DNA. Lys7 and Tyr peptides with +4/+5 charges indicate cooperative binding with pDNA without saturation of interaction while Val2-Gly-Lys4, Val-Gly-Lys5, and Phe-Gly-Lys5 lead to saturation of interaction indicating condensed pDNA within the range of N/Ps studied. We show that the biophysical properties of DNA-peptide complexes could be modulated by design and the peptides presented here could be used as building blocks for creating DNA-peptide complexes for various biomedical applications, mainly nucleic acid delivery.

KEYWORDS: Plasmid DNA, amphiphilic peptides, hydrodynamics, thermodynamics, zeta potential

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