Targeting lipopolyplexes using bifunctional peptides incorporating hydrophobic spacer amino acids: synthesis, transfection, and biophysical studies.
We have developed efficient synthetic routes to two hydrophobic amino acids, suitably protected for solid-phase peptide synthesis, and have successfully synthesized peptides containing these or other hydrophobic amino acids as spacers between a Lys16 moiety and an integrin-targeting motif. These peptides have in turn been used to formulate a range of lipopolyplex vectors with Lipofectin and plasmid DNA. The transfection efficiencies of these vectors and their aggregation behavior in buffers and in serum have been studied. We have shown that vectors containing peptides incorporating long linkers that are entirely hydrophobic are less efficient transfection agents. However, linkers of equivalent length that are in part hydrophobic show improved transfection properties, which is probably due to the improved accessibility of the integrin-binding motif.
Pilkington-Miksa
Michael A
MA
Department of Chemistry, University College London, Christopher Ingold Laboratories, London, UK.
Writer
Michele J
MJ
Sarkar
Supti
S
Meng
Qing-Hai
QH
Barker
Suzie E
SE
Shamlou
Parviz Ayazi
PA
Hailes
Helen C
HC
Hart
Stephen L
SL
Tabor
Alethea B
AB
D000596:Amino Acids / Q000737:chemistry*; D055592:Biophysical Phenomena; D001703:Biophysics; D003432:Cross-Linking Reagents / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010316:Particle Size; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
D000596:Amino Acids; D003432:Cross-Linking Reagents; D008055:Lipids; D010455:Peptides