An Amphiphilic Peptide Carrier for HCl Transport

Abstract

Single molecules that co‐transport cations as well as anions across lipid membranes are few despite their high biological utility. The elegant yet simple lipidomimmetic peptide design herein enables efficient HCl transport without the use of any external additives for proton transport. The carboxylic acids in the dipeptide scaffold provide a handle to append two long hydrophobic tails and also provide a polar hydrophilic carboxylate group. The peptide central unit also provides NH sites for anion binding. Protonation of the carboxylate group coupled with the weak halide binding of the terminal NH group results in HCl transport with transport rates of H+>Cl−. The lipid‐like structure also facilitates seamless membrane integration and flipping of the molecule. The biocompatibility, design simplicity, and potential pH regulation of these molecules open up several avenues for their therapeutic use.

Naphthalimide-based, Single-Chromophore, Ratiometric Fluorescent Sensor for Tracking Intracellular pH

“…11 A time-lapse imaging experiment in the absence of the peptide at pH 7 4. showed no change in emission proving the photostability of TRapH (Fig S13).…”

“…Both TRapH and protonated TRapH could be excited at 405 nm (Fig S8) since both species showed some absorption at this wavelength. Before proceeding with the in-cell studies, Since TRapH, showed a ratiometric response between a pH range of 3-6, we next decided to apply a previously established peptide-based synthetic H + ion transporter, Amphiphilic Peptide 1a (Fig S12 ), 11 to HeLa cells to reduce intracellular pH, and record temporal pH changes live (Fig 4). Amphiphilic Peptide 1a, has been reported to reduce pH inside vesicles via transport of H + ions.…”