Sterol−Polyamine Conjugates as Synthetic Ionophores

Abstract

A design principle has been devised for the construction of sterol−polyamine conjugates that function as synthetic ionophores. For feasibility studies, a prototype (1) was synthesized from 3β-hydroxybisnor-5-cholenic acid via sequential activation of its carboxylic acid moiety, condensation with spermine, and sulfation of the 3β-hydroxyl group. Closely related analogues were also prepared in which the terminal amine group was acetylated (2), the 3β-hydroxyl group was left unsulfated (3), and each of the two remaining secondary amines was replaced with oxygen atoms (4). Incorporation of each conjugate into egg phosphatidylglycerol-based vesicles showed that 1 functions as an ionophore by discharging a pH difference across the vesicle membrane, but that 2, 3, and 4 do not. A kinetic analysis of the ionophoric activity of 1 has provided evidence that the majority of the conjugate exists as membrane-bound monomer and that dimers are the active species that are responsible for ion transport. Comparative experiments have also shown that 1 exhibits greater activity in negatively charged phospholipid membranes relative to ones that are electrically neutral. The implications of these findings, with regard to the design of new classes of antibacterial agents, are briefly discussed.

Aminobenzoic acid incorporated octapeptides for cation transport

“…2 illustrates the relationship between the observed k values and peptide concentration. 27 In this equation, n corresponds to the number of peptide units that interact with a single ion and K corresponds to the equilibrium for peptide aggregate-monomer dissociation. Since a background transport is observed with DMSO, the dependence of k with concentration is given by Eq.…”

Increasing pH Causes Faster Anion‐ and Cation‐Transport Rates through a Synthetic Ion Channel

“…[11] In order to compare the transport rates at different pH values, the channel concentration was kept constant. Thus, Equation (1) …”

Artificial Anion Transporters in Bilayer Membranes

“…The inner surface of the pore is lined by the polyamine chain which can serve as a conduit for ion transport, whereby each protonable nitrogen may function as a "relay" element that moves protons and/or anions across the lipid bilayer. Combined experimental evidences from 23 Na + -NMR and HPTS assay, excluded transport of sodium ion and confirmed the ability to transport chloride through a H + /Cl -symport (or the kinetically equivalent OH -/Cl -antiport) [56]. Hill coefficients indicated that the active specie is a dimer and control experiments with compounds missing one of the two polar head groups demonstrated their importance for the activity.…”