Activity-Structure Study on the Peptide Fraction of AG2: a Potent In Vitro Transfection Agent

Abstract

Gemini-based amphiphiles are candidates for biomedical applications. In fact, most of thegemini compounds described in the literature have been prepared to be used as new syntheticvectors in gene transfection. Our group carried out an activity-structure study starting from thestructure of the gemini [AG2-C18/]2, which is an effective in vitro transfection reagent. Wesynthesized a series of novel amphiphilic amino acid derivatives of low molecular weight,named AGn-Cm(N), in which the same apolar region (m) of oleic or palmitic acid wasmaintained and the peptide region was modified by amino acid insertions, deletions, andsubstitutions. We also determined the transfection efficiency, critical micelle concentration,particle size, and ζ-potential for these derivatives. Amphiphiles AG10-C16and AG 10-C18weremore active at a lower N/P ratio than AG2-C18. These amphiphiles showed no activity whenlysine was replaced by ornithine, and the activity of all derivatives increased when there weremore ornithine residues and a W/O = 1 ratio in the peptide region. It can be said that for AG10-C16, these two structural requirements on the amino acid portion predominated over the type ofaliphatic chain used.