# Anion-Binding Properties of Short Linear Homopeptides

## TL;DR

This study explores how short phenylalanine peptides bind to anions and change shape, which could help in making cyclopeptides and transporting ions across membranes.

## Contribution

The study reveals how anion binding induces structural changes in peptides, aiding cyclopeptide synthesis and ion transport.

## Key findings

- All three peptides formed 1:1 complexes with chloride, bromide, hydrogen sulfate, DHP, and nitrate anions.
- Anion binding caused peptides to shift from elongated to quasi-cyclic conformations, aiding ring closure in cyclopeptide synthesis.
- Peptides can act as ionophores, enabling transmembrane anion transport.

## Abstract

A comprehensive thermodynamic and structural study of the complexation affinities of tetra (L1), penta (L2), and hexaphenylalanine (L3) linear peptides towards several inorganic anions in acetonitrile (MeCN) and N,N-dimethylformamide (DMF) was carried out. The influence of the chain length on the complexation thermodynamics and structural changes upon anion binding are particularly addressed here. The complexation processes were characterized by means of spectrofluorimetric, 1H NMR, microcalorimetric, and circular dichroism spectroscopy titrations. The results indicate that all three peptides formed complexes of 1:1 stoichiometry with chloride, bromide, hydrogen sulfate, dihydrogen phosphate (DHP), and nitrate anions in acetonitrile and DMF. In the case of hydrogen sulfate and DHP, anion complexes of higher stoichiometries were observed as well, namely those with 1:2 and 2:1 (peptide:anion) complexes. Anion-induced peptide backbone structural changes were studied by molecular dynamic simulations. The anions interacted with backbone amide protons and one of the N-terminal amine protons through hydrogen bonding. Due to the anion binding, the main chain of the studied peptides changed its conformation from elongated to quasi-cyclic in all 1:1 complexes. The accomplishment of such a conformation is especially important for cyclopeptide synthesis in the head-to-tail macrocyclization step, since it is most suitable for ring closure. In addition, the studied peptides can act as versatile ionophores, facilitating transmembrane anion transport.