Aggregation Behavior and Dynamics of Synthetic Amphiphiles That Self‐Assemble to Anion Transporters

Abstract

The amphiphilic heptapeptides-referred to as synthetic anion transporters (SATs)-mediate chloride transport in planar lipid bilayer membranes, synthetic liposomes, and mammalian cells. The SATs described have the general formula R1(2)NCOCH2OCH2CO-(Gly)3-Pro-(Gly)3-OR2. Substitution at R1 and R2 with various aliphatic or aromatic groups alters the ability of SATs to transport chloride through a phospholipid bilayer membrane. Despite extensive structure-activity relationship studies concerning Cl(-)-mediated transport by SATs, relatively little was known about the mechanism of insertion and pore-formation in the membrane. In the current study, the mechanistic behavior of SATs was investigated in aqueous solution and at the air-water interface. In the latter case, Langmuir trough studies and Brewster angle microscopy (BAM) revealed the extent of monolayer stability and organization for SATs. Dynamic light scattering and transmission electron microscopy (TEM) confirmed these results and defined the aggregation behavior of SATs in solution. SAT derivatives that showed low chloride transport activity organized into stable monolayers at the air-water interface, while more active SATs formed less stable monolayers. The relationship between intermolecular organization of SATs and pore-formation in the membrane is discussed along with its implications for chloride transport.

Amino acid containing anion receptors

“…34 Recent investigations also involve the elucidation of the mechanism of insertion and pore formation of these synthetic anion transporters in the membrane by using methods such as Langmuir trough studies, Brewster angle microscopy, dynamic light scattering, and transmission electron microscopy. 35,36 Since activity in chloride transport requires the peptide to specifically, if only transiently, interact with this anion, NMR spectroscopic binding studies in CDCl 3 using 1a and related compounds were performed. 37,38 These investigations were based on the observation that characteristic shifts of the NH signals are induced in the 1 H NMR spectrum of 1b, a derivative of 1a with shortened N-terminal anchor chains, by the presence of Bu 4 NCl (Chart 1).…”

Aggregation and Supramolecular Membrane Interactions that Influence Anion Transport in Tryptophan‐Containing Synthetic Peptides

“…We previously reported reproducible phase transitions at (176 AE 6) and (68 AE 4) nm for GGG . [30] Similar studies were conducted as part of this work with WGG, wGG, GWG, and GGW. The trough experiments were replicated as many as 12 times for each amphiphile in a failed effort to achieve reproducibility.…”

“…We previously observed bimodal distributions for related ionophores that had C-terminal benzyl rather than n-heptyl esters only by DLS, but could not confirm them by microscopy. [30] The right panel of TEM Figure 3 shows spherical aggregates (ca. 30-70 nm) of WGG that correspond to the smaller size in the bimodal distribution.…”

Anion transport and binding properties of N N′-(phenylmethylene)dibenzamide based receptors

“…This would allow the slow start to transport to be rationalised, as delivery through the aqueous external solution is hindered. Another explanation of the unusual concentration dependant results is the possibility of self-aggregation of the receptors in solution which is reported to be counterproductive to transport efficacy (27,28).…”