In 2019 Lee et al. developed helical poly-L-lysine peptides conjugated with trimethylammonium and crown ether moieties to achieve potassium transport and induce endoplasmic reticulum stress-mediated apoptosis. These molecules acted as selective K⁺ ionophores and exhibited antitumoral activity. In 2020, Madhavan's group designed low molecular weight cation-selective carriers based on di- to tetrapeptides equipped with aminobenzoic acid and L/D-alanine, which were able to transport cations through an antiport M⁺/H⁺ or symport M⁺/OH⁻ mechanism. Due to their tuneable yet simple structures, peptides can also be used as scaffolds for enhancing ion transport activity and selectivity. More recently, the same group designed a new lipidomimetic peptide for HCl transport, which comprises two aspartate residues bearing three carboxylate units, two of them to append long alkyl chains and a free one as a polar hydrophilic group. The anion binds to the NH groups of the peptide, and the lipid-like structure facilitates membrane integration and flipping. The resulting carriers exhibit H⁺ > Cl⁻ >> M⁺ selectivity, probably due to the protonation of the free carboxylate and the weak halide-binding ability of the NH groups.

In indiependent work, Madhavan and colleagues approached an ion pair co-transport system by using simple cyclic dipeptides with ester motif pendants. The designed molecules had the ability to co-transport M⁺/X⁻ ions through a symport mechanism with potassium selectivity. The NH groups in the peptide scaffold favour the interaction with Cl⁻, while the carbonyl and ester linkages interact with K⁺ and H⁺.  The unique supramolecular properties of D, L-cyclic peptides make them interesting scaffolds for the design of new ion transport systems. In 2020, Fuertes et al. designed dimeric symport ionophores based on pyridine-decorated cyclic peptides. The α,γ-cyclic peptide scaffold provided the right topological disposition for the three pyridine moieties to coordinate ions. In the proposed transport mechanism, besides the expected cation recognition, pyridine units simultaneously coordinated with anions through anion-π interactions or hydrogen bonds, having the same recognition motif for both ions.

Anion selectivity could be tuned by changing the pyridine isomer appended to the cyclic peptide. In subsequent work, they used similar α,γ-cyclic peptide scaffolds that were functionalized with flexible pendants to obtain dimeric membrane-spanning ionophores. These flexible pendants incorporated polar end groups that could reach both membrane sides, inducing a transient permeable state. A small library of oligoethylene glycol-based moieties were attached to the cyclic peptide scaffold via click chemistry, leading to a library of compounds providing different transport behaviours. The same group later exploited a similar cyclic peptide backbone for the generation of dimeric supramolecular capsules that entrapped hydrated anion clusters by the addition of tris(triazolyethyl)amine caps attached to a central peptide scaffold. The resultant supramolecular capsules were also able to transport Cl⁻ across phospholipid bilayers through a symport H⁺/Cl⁻ or antiport OH⁻/Cl⁻ mechanism (see Pérez-Pérez et al. 2025 for details and the original references.