# Transmembrane Transport of cAMP and AMP Using a Two Component Small Molecule Transport System

## TL;DR

Scientists developed a system to transport cAMP and AMP across cell membranes using two small molecules, which could help in drug delivery and synthetic biology.

## Contribution

The first example of facilitated transport of cAMP and AMP across membranes using a two-component small molecule system.

## Key findings

- A fluorinated squaramide effectively transports cAMP without a thymine derivative.
- The two-component system enables transmembrane nucleotide transport without damaging the membrane.
- 31P NMR and fluorescence experiments confirmed successful nucleotide transport.

## Abstract

Nucleotides such as cAMP (cyclic adenosine monophosphate) and AMP (adenosine monophosphate) are central to many cellular processes, but their highly hydrophilic and charged nature prevents passive permeation across lipid bilayers. Here, we report the first example of facilitated transport of cAMP and AMP across liposome membranes using a neutral two‐component system at physiological pH. This system pairs a synthetic anionophore targeting the phosphate group with a thymine derivative to boost transport efficiency. Liposome‐based fluorescence and 31P NMR experiments confirmed transmembrane transport, supported by control experiments. A fluorinated squaramide proved to be the best transporter and was able to transport cAMP even without the help of a thymine derivative, as well as AMP in the presence of a lipophilic thymine derivative. These findings show that carefully designed small molecules can enable direct nucleotide translocation, with potential applications in drug delivery and synthetic biology.

Transmembrane transport of the nucleotides cAMP (cyclic adenosine monophosphate) and AMP (adenosine monophosphate) is challenging, but can be achieved using a two‐component system consisting of a synthetic anionophore (e.g., squaramides) and a lipophilic thymine derivative. Fluorescence and NMR‐based liposomes studies confirm that direct translocation of the nucleotides across the membrane occurs without disruption of membrane integrity.