Receptors for High-Affinity Binding in Water

Abstract

Achieving ultrahigh binding constants(K_a > 10⁹ M^-1) and bioorthogonal selectivity in water is a significant research challenge in the field of supramolecular chemistry. One of the strongest interactions in nature, the binding between biotin and (strept)avidin (K_d up to 10^-15 M), has been used to non-covalently link molecules together, finding several applications in medicine, biotechnology, and molecular engineering. Synthetic alternatives to this system (“synthavidin” technology) could be used in a similar way for molecular bioconjugation and the development of non-covalent click chemistry.
Within this body of work, the possibility of employing a group of “temple” receptors (characterised by two aromatic surfaces held apart by rigid polar spacers) for the development of new synthavidin systems has been investigated. The binding to a range of dye molecules, small aromatic guests, and carbohydrates has been studied providing useful insights about the binding properties of these receptors in water.
Anthracene macrocyclic receptor-squaraine dye systems have previously been shown to be promising alternatives to the biotin-(strept)avidin system for imaging applications. Here the replacement of the anthracene moieties with tetraoxapentacene was found to increase affinities towards squaraine dyes and improve selectivities. Promising results were also obtained from the interaction between pyrene-pyrene octalactam receptors and naphthalenediimides (NDIs), with binding constants up to 2.1 x 10⁷ M^-1 observed.

Date of Award	23 Jan 2024
Original language	English
Awarding Institution	University of Bristol
Supervisor	Anthony P Davis (Supervisor) & Varinder K Aggarwal (Supervisor)