Understanding Noncovalent Interactions in the Binding of Phosphate and Sulfate Oxoanions with Peptide-based Receptors: A Computational Approach

Abstract

Recognition of anions with natural and synthetic receptors has become an important topic across many fields. Because anions play key roles in both biological systems and the environment, there is a growing need for receptors that can select them out accurately and efficiently. This creates a strong motivation to develop receptors that are simple to use, affordable, and able to form stable and selective interactions with specific anions. Peptide-based receptors are useful in this area because their flexible structures and directional noncovalent interactions make them well-suited for binding oxyanions. Peptidomimetics enhance the stability and flexibility of the peptide backbone through structural modifications, cyclisation, and the introduction of non-natural amino acids, thereby enabling these systems to be finely tuned for selective anion binding. The present thesis applies these methods to investigate the fundamental binding mechanisms of dipeptides, tetrapeptides, and their peptidomimetic derivatives toward dihydrogen phosphate (𝐻2𝑃𝑂4−) and hydrogen sulfate (𝐻𝑆𝑂4−) anions. The insights gained from this work lay the groundwork for designing tailored receptors with potential applications in anion sensing, separation, and environmental monitoring.