Cation‐Transporting Peptides: Scaffolds for Functionalized Pores?

Abstract

Protein pores that selectively transport ions across membranes are among nature's most efficient machines. The selectivity of these pores can be exploited for ion sensing and water purification. Since it is difficult to reconstitute membrane proteins in their active form for practical applications it is desirable to develop robust synthetic compounds that selectively transport ions across cell membranes. One can envision tuning the selectivity of pores by incorporating functional groups inside the pore. Readily accessible octapeptides containing (aminomethyl)benzoic acid and alanine are reported here that preferentially transport cations over halides across the lipid bilayer. Ion transport is hypothesized through pores formed by stable assemblies of the peptides. The aromatic ring(s) appear to be proximal to the pore and could be potentially utilized for functionalizing the pore interior.

Ligand Induced CuII Transport Restricts Cancer and Mycobacterial Growth: Towards a Plug‐and‐Select Ion Channel Scaffold

“…1‐Ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide (EDC) and N , N ‐dimethylpyridine‐4‐amine (DMAP) were used for all coupling reactions (Scheme 1). Pybox 4 was coupled with acetic acid to give the corresponding ester, which was coupled with tripeptide 5 [6b] to give peptide 1 in 52 % yield, over two steps. Pybox 4 was sequentially coupled with myristic acid and tripeptide 5 to give peptide 2 in 28 % yield, over two steps.…”

Optimizing the Readout of Lanthanide-DOTA Complexes for the Detection of Ligand-Bound Copper(I)

“… Picolinate-derivatized ligands have previously been shown to act as sensitizers for europium and terbium ions [ 32 , 33 , 34 , 35 ], to undergo cellular entry via diffusion, and to be suitable for two photon excitation studies. Thus picolinate azides 6 – 9 were prepared from pyridine-2,6-dicarboxylic acid dimethyl ester through ready adaptation of the synthetic route to the 10-coordinate N , N , N ′, N ′-tetrakis[(6-carboxypyridin-2-yl)methyl]ethylenediamine (tpaen) ligand reported by Mazzanti et al [ 33 , 36 , 37 ] ( SM Scheme S2 ; three steps (28% overall), four steps (15% overall), three steps (27% overall), and four steps (22% overall) respectively). Lanthanide complexes based on coumarin derivatives were pursued due to the known membrane permeability of coumarin azides [ 38 ], and previous reports of strong fluorescence activation of lanthanides by coumarin [ 39 , 40 , 41 , 42 ].…”

Cation–halide transport through peptide pores containing aminopicolinic acid

“…[35][36][37] The replacement of aromatic units in peptide scaffold 4 with aminomethyl pyridyl units was shown to significantly enhance its cation transport activity. 37 Inspired by these observations, we designed peptide 2 that incorporates aminopicolinic acid units into our most active peptide scaffold 3 that we believe forms tetrameric pores. 35,36 We envisioned that the pyridyl rings would significantly enhance the cation transport activity of peptide 2.…”