The starting point of this study is the solid state structure of a complex between human carbonic anhydrase II (HCAII) and a helically folded tetradecaamide aromatic foldamer with a nanomolar HCAII li...

Helical aromatic oligoamide DNA mimic foldamers that reproduce the shape and charge distribution of duplex B-DNA have been interfaced with DNA duplexes by means of a new linker that serves both as a ...

Helical aromatic oligoamide foldamers with a cluster of five biogenic side chains at their surface were designed and synthesized. Display selection of thioether macrocyclic peptides against these targ...

Aromatic oligoamides, with their intrinsic rigidity and well-defined conformations, are recognized for their potential in medical applications. Similar structures are present in several naturally occurring antibiotics and have been explored for their ability to bind to various proteins and B-DNA (canonical right-handed DNA helix). This study introduces a synthetic approach to produce quinoline amino acid monomers bearing diversified side chain combinations in positions 4, 5, and 6 of the quinoline ring, designed to enhance the side chain density on helical foldamers. By increasing the number of side chains on each monomer, we aim to mimic the dense side chain presentation of α-peptides, thus improving the potential for protein surface recognition. This synthetic strategy involves efficient functionalization through cross-coupling reactions, enabling the installation of diverse side chains at strategic positions on the quinoline ring. The process has been optimized for automated solid-phase synthesis, successfully producing a 20-unit oligoamide with good purity. This foldamer, featuring multiple cationic, anionic, polar, and hydrophobic side chains, demonstrates the potential for molecular recognition in drug discovery and therapeutic applications. The methodology described here represents a significant advancement in the construction of aromatic oligoamide foldamers, providing a robust platform for further exploration of biological systems.

Biomolecular mimics are intended to outperform their natural counterparts. However, B-DNA surface mimicry to target DNA-binding proteins has long remained underdeveloped. We have introduced helical a...

A biotinylated helical aromatic oligoamide foldamer equivalent in size to a 24mer peptide was designed without any prejudice other than to display various polar and hydrophobic side chains at its surf...