Authors:
JG Harrison, S Balasubramanian
Journal name: 
Nucleic Acids Res
Citation info: 
26(13):3136-3145
Abstract: 
A small library of 49 peptide-oligonucleotide conjugates were synthesized to explore the influence of various peptide side chains on the hybridization properties of the DNA. An invariant 8mer oligonucleotide was coupled to a peptide portion that contained a five residue variable region composed of the cationic amino acids lysine, ornithine, histidine and arginine, the hydrophobic amino acid tryptophan, and alanine as a spacer. Melting temperature analysis indicated that T m depended principally on the number of cationic residues. The free energies of binding for polycationic peptide-oligonucleotides were enhanced compared with the unmodified 8mer. The origin of this stabilizing effect was found to be derived from a more exothermic enthalpic term. Improvement in Delta G vH was found to depend on the presence of positive charge and also the exact identity of the cationic amino acid, with the polyarginine peptide giving the most favourable Delta G vH value and the most exothermic Delta H vH. Further exploration suggested that the cationic peptide fragments interacted mainly with single-stranded rather than duplex DNA. A study of pH dependence showed that the polyhistidine conjugate was particularly sensitive to pH changes near neutrality, as indicated by a significant rise in T m from 19.5 degrees C at pH 8.0 to 28.5 degrees C at pH 6.0.
DOI: 
http://doi.org/10.1093/nar/26.13.3136
Research group: 
Balasubramanian Group
E-pub date: 
30 Jun 1998
Users with this publication listed: 
Shankar Balasubramanian