TY - JOUR
T1 - Effect of the amino acid composition of cyclic peptides on their self-assembly in lipid bilayers
AU - Danial, Maarten
AU - Perrier, Sebastien Paul Edmond
AU - Jolliffe, Katrina A
PY - 2015
Y1 - 2015
N2 - The effect of amino acid composition on the formation of transmembrane channels in lipid bilayers upon self-assembly of alt-(l,d)-a-cyclic octapeptides has been investigated. Cyclic peptides comprising d-leucine, alternating with different combinations of l-azidolysine, l-lysine(Alloc), l-lysine and l-tryptophan were synthesized and the size of pores formed via self-assembly of these molecules in lipid bilayers was elucidated using large unilamellar vesicle fluorescence assays and dynamic light scattering. Pore formation was examined in large unilamellar vesicles made up of egg yolk phosphatidylcholine or Escherichia coli total lipid extract. From these analyses, we have established that cyclic peptides with charged side chains form large pores while those with neutral side chains form unimeric pores. Furthermore, the cyclic peptides that consist of non-symmetric amino acid configurations possess a higher membrane activity than the cyclic peptides with a symmetric amino acid configuration. In addition, we have found that peptide amphiphilicity plays a vital role in selective partitioning between bilayers that consist of egg yolk phosphatidylcholine and those comprised of E. coli total lipid extract. These results suggest that selective transbilayer channel formation via self-assembly may be a viable alternative for many applications that currently use more expensive, multistep synthesis methods.
AB - The effect of amino acid composition on the formation of transmembrane channels in lipid bilayers upon self-assembly of alt-(l,d)-a-cyclic octapeptides has been investigated. Cyclic peptides comprising d-leucine, alternating with different combinations of l-azidolysine, l-lysine(Alloc), l-lysine and l-tryptophan were synthesized and the size of pores formed via self-assembly of these molecules in lipid bilayers was elucidated using large unilamellar vesicle fluorescence assays and dynamic light scattering. Pore formation was examined in large unilamellar vesicles made up of egg yolk phosphatidylcholine or Escherichia coli total lipid extract. From these analyses, we have established that cyclic peptides with charged side chains form large pores while those with neutral side chains form unimeric pores. Furthermore, the cyclic peptides that consist of non-symmetric amino acid configurations possess a higher membrane activity than the cyclic peptides with a symmetric amino acid configuration. In addition, we have found that peptide amphiphilicity plays a vital role in selective partitioning between bilayers that consist of egg yolk phosphatidylcholine and those comprised of E. coli total lipid extract. These results suggest that selective transbilayer channel formation via self-assembly may be a viable alternative for many applications that currently use more expensive, multistep synthesis methods.
UR - http://pubs.rsc.org/en/content/articlepdf/2015/ob/c4ob02041c
U2 - 10.1039/c4ob02041c
DO - 10.1039/c4ob02041c
M3 - Article
SN - 1477-0520
VL - 13
SP - 2464
EP - 2473
JO - Organic & Biomolecular Chemistry
JF - Organic & Biomolecular Chemistry
IS - 8
ER -