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

Nine amphiphilic heptapeptides, synthetic anion transporters (SATs) of the form(C18H37)(2)N-Y-(Gly)(3)-Pro-(Gly)(3)-OCH2Ph were prepared. The unit (OH2) 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 (C18H37)(2)N-(Gly)(3)-Pro-(Gly)(3)-OCH2Ph or (C18H37)(2)N-(Gly)(4)-Pro-(Gly)(3)-OCH2Ph. The diglycolic acid derivative was reported previously but the remaining compounds are new. These nine peptides mediated release of Cl- from DOPC/DOPA vesicles with varying efficacy. Chloride release diminished for the Y-containing amphiphilic heptapeptides in the order glutaric, succinic > 3-thiaglutaric > terephthalic > acetic, N-methyliminodiacetic, > no Y, isophthalic. The release of Cl- 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- 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.