Pore-Forming Monopeptides as Exceptionally Active Anion Channels

Abstract

We describe here a unique family of pore-forming anion-transporting peptides possessing a single-amino-acid-derived peptidic backbone that is the shortest among natural and synthetic pore-forming peptides. These monopeptides with built-in H-bonding capacity self-assemble into an H-bonded 1D columnar structure, presenting three types of exteriorly arranged hydrophobic side chains that closely mimic the overall topology of an α-helix. Dynamic interactions among these side chains and membrane lipids proceed in a way likely similar to how α-helix bundle is formed. This subsequently enables oligomerization of these rod-like structures to form ring-shaped ensembles of varying sizes with a pore size of smaller than 1.0 nm in diameter but sufficiently large for transporting anions across the membrane. The intrinsic high modularity in the backbone further allows rapid tuning in side chains for combinatorial optimization of channel's ion-transport activity, culminating in the discovery of an exceptionally active anion-transporting monopeptide 6L10 with an EC of 0.10 μM for nitrate anions.

Apoptosis-inducing activity of a fluorescent barrel-rosette M+/Cl− channel

“…To see if there is any role of anions involved in the transport process, the anion selectivity study was performed by varying the intravesicular and extravesicular anions of NaX salts (X À ¼ Cl À , Br À , I À , NO 3 À , and ClO 4 À ), and changes in the ion transport rate were checked upon applying a pH gradient of 0.8 (pH in ¼ 7.0 and pH out ¼ 7.8). 48,51,52 Interestingly, the data conrmed a considerable selectivity of the channel towards Cl À compared to the other anions (Fig. 3B).…”

Polyhydrazide‐Based Organic Nanotubes as Efficient and Selective Artificial Iodide Channels

“…Next, SPQ [6‐methoxy‐ N ‐(3‐sulfopropyl)quinolinium] whose fluorescence intensity decreases in the presence of increasing concentrations of Cl − was introduced into extravesicular region of LUVs (Figure f) . The observed concentration‐dependant quenching of SPQ for channel 1 a at 0.2–1.0 μ m provides direct proof of 1 a ‐mediated chloride influx into LUV.…”

“…To additionally differentiate the transport rates between Cl − and OH − or H + , proton transporter FCCP was applied in the HPTS assay (Figure g) . That transport activities of 1 a (0.5 μ m ) were found to be comparable in either the presence (49 %) or absence (50 %) of FCCP suggests H + or OH − transport rates to be faster than that of Cl − , which constitutes the rate‐limiting step.…”

“…To additionally differentiate the transport rates between Cl À and OH À or H + ,proton transporter FCCP was applied in the HPTS assay (Figure 2g). [18] That transport activities of 1a (0.5 mm)were found to be comparable in either the presence (49 %) or absence (50 %) of FCCP suggests H + or OH À transport rates to be faster than that of Cl À ,which constitutes the rate-limiting step.F urther,m olecular dynamics (MD) results clearly point to the formation of the water chains (see Supporting movie SM3), and these water chains should facilitate rapid transport of H + ,n ot OH À ,b yt he Grotthuss mechanism across membranes to maintain the charge balance.…”

Low Molecular Weight Di‐ to Tetrapeptide Transmembrane Cation Transporters

“…[ 17 ] Recently Zheng and co‐workers developed the smallest monopeptidic and tripeptidic anion channels containing long alkyl chains at the C and N termini. [ 18 ] While there are several examples of synthetic anion transporters, only a few low molecular weight cation transporters have been reported in the past decade. [ 19 ]…”