Influence of N-terminal hydrophobicity of cationic peptides on thermodynamics of their interaction with plasmid DNA.
There is a need to understand the thermodynamics of interaction of cationic peptides with DNA to design better peptide based non-viral gene delivery vectors. The main aim of this study was to understand the influence of N-terminal hydrophobicity of cationic amphiphilic peptides on thermodynamics of interaction with plasmid DNA. The model peptides used were TATPTD and TATPTDs modified at the N-terminal with hydrophobic amino acids. The thermodynamic binding data from isothermal titration calorimetry were compared with ethidium bromide analysis and ultrafiltration to correlate the binding parameters with the structural features of the various peptides used. It was observed that peptides having a smaller hydrophobic domain at the N-terminal have good DNA condensing ability compared with the ones with a longer hydrophobic domain. Calorimetry of peptides that reached saturation binding indicated that enthalpy and entropy are favorable for the interaction. Moreover, the interaction of these peptides with DNA appears to be predominantly electrostatic.
Department of Pharmaceutical Sciences, University of the Sciences in Philadelphia, Philadelphia, PA 19104, USA.
Geetha N
GN
Goparaju
Michael F
MF
Bruist
C Satish
CS
Chandran
Pardeep K
PK
Gupta
D000595:Amino Acid Sequence; D002151:Calorimetry; D002412:Cations; D004247:DNA / Q000737:chemistry*; D004996:Ethidium / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry*; D011485:Protein Binding; D013816:Thermodynamics
D002412:Cations; D010455:Peptides; D004247:DNA; D004996:Ethidium