Sequence defined foldamers for the synthesis of β-strand mimetics and macrocycles

Abstract

Using Nature as divine inspiration, we looked towards synthesising unnatural, man-made foldamers. These molecules are able to adopt a well-defined structure, capable or replicating or selectively inhibiting some of Nature’s most important biological interactions. Chapter 1: Introduces the concept of foldamers and how they relate to peptide secondary and tertiary structure. This chapter will be focused solely on reviewing the most important and exciting literature in the field. Chapter 2: Focuses on the synthesis of a 1,3-linked pyrrolinone β-strand mimic that can project R-group substituents both above and below the plane. These compounds were designed with the selective interruption of protein-protein interactions in mind. The conformation of these structures was held in place by dipolar repulsion, and the bias confirmed through NMR spectroscopy and X-ray crystallography. Chapter 3: Develops a series of macrocyclic foldamers capable of reversibly binding cations. The macrocycles were synthesised by solution phase, solid phase and self-assembly methods, with the former two methods allowing for the synthesis of a fully sequence-defined macrocycle. The structure of the macrocycles were also controlled via dipolar repulsion and confirmed by NMR spectroscopy and X-ray crystallographic analysis.

Date of Award	Jul 2024
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Northern Ireland Department for the Economy
Supervisor	Peter Knipe (Supervisor) & Paul Stevenson (Supervisor)