The effect of midpolar regime mimics on anion transport mediated by amphiphilic heptapeptides

Abstract

Nine amphiphilic heptapeptides, synthetic anion transporters (SATs) of the form (C 18 H 37 ) 2 N-Y-(Gly) 3 -Pro-(Gly) 3 -OCH 2 Ph were prepared. The unit (OH 2 )Y represents the diacids succinic, glutaric, diglycolic, 3-thiaglutaric, N-methyliminodiglycine, isophthalic, and terephthalic acids. Additionally, Y was absent or present as acetic acid affording the structure (C 18 H 37 ) 2 N-(Gly) 3 -Pro-(Gly) 3 -OCH 2 Ph or (C 18 H 37 ) 2 N-(Gly) 4 -Pro-(Gly) 3 -OCH 2 Ph. The diglycolic acid derivative was reported previously but the remaining compounds are new. These nine peptides mediated release of Cl À from DOPC/DOPA vesicles with varying efficacy. Chloride release diminished for the Y-containing amphiphilic heptapeptides in the order glutaric, succinic 4 3-thiaglutaric 4 terephthalic 4 acetic, N-methyliminodiacetic, 4 no Y, isophthalic. The release of Cl À was generally exponential over time but the curve shapes were distinctly sigmoidal for the more flexible diacids. Computational studies were undertaken to assess differences in conformation. Overall, it appeared that Cl À release for those SATs that could adopt a linear conformation on the N-terminal side of proline correlated best with the polarity of the diacid.

Polymer‐Induced Transient Pores in Lipid Membranes

“…[11] An important structural feature for most pore-forming molecules is the necessity to accommodate the hydrophobic lipid bilayer structure inside the membrane, but to still keep sufficient hydrophilicity on the outside of the membrane to allow the open state of the final pore. [13] Thus, simple lipids clustering within a membrane, such as C 2 and C 16 ceramides, can also generate large stable pores within a membrane. [14] Apart from these structurally highly defined organic molecules, unfolded synthetic macromolecules have shown similar pore-formation abilities upon contact with lipid bilayer membranes, although their final structure is less predictable.…”

Polymerinduzierte transiente Poren in Lipidmembranen

“…Häufig wiederkehrende Strukturelemente, die diese Moleküle innerhalb der Membran einnehmen, sind Zylinderformen mit supramolekularen Elementen wie Helices, flüssigkristallinen Stapeln,7 “Barrel‐Hoop”‐12 und “Barrel‐Rossette”‐Poren 11. Ein häufiges Strukturmerkmal ergibt sich daraus, dass der hydrophobe Teil der Moleküle in der Lipidmembran verankert sein muss, ohne jedoch die Hydrophilie der Membrangrenzen zu stark zu beeinträchtigen, sodass offene Poren ausgebildet werden können 13. Auf diese Weise können auch einfache Lipide wie C 2 ‐ und C 16 ‐Ceramide unter Bildung großer stabiler Poren in die Membran eingebaut werden 14…”

Artificial Anion Transporters in Bilayer Membranes

“…Chloride binding to the peptide was proved by NMR studies [34,35], moreover, two covalent dimers were synthesized to confirm the indications that the active complex was dimeric [36]. The role of the different subunits was investigated by systematic variation of the peptide sequence [37,38], peptide length [39], midpolar regime mimic [40], C-terminal anchor and N-terminal dialkylamine residue [41]. The emerging picture is rather complex and while the presence of the proline is clearly essential for activity (thanks to its effect on the peptide conformation), the effect of other structural variations is less straightforward.…”