The Waters group is interested in understanding how biomolecules recognize each other with both high affinity and high selectivity. Our overall goal is to design molecules to control biomolecular recognition for biomedical applications. This requires a detailed knowledge of noncovalent interactions in water. Our research combines aspects of organic chemistry, including synthesis, molecular recognition, and supramolecular chemistry, with biochemistry and biophysics.
Our group is designing small, structured peptides as mimics for protein domains. We aim to develop peptide-based receptors for a number of biological molecules, including small molecules, DNA, RNA, and proteins. In some cases, we utilize unnatural amino acids to gain affinity selectivity for the desired target.
Post-translational modifications are covalent modifications of proteins that act as signaling mechanisms within the cell. We are studying how such modifications trigger protein-protein interactions. In addition, we are using these modifications to develop synthetic molecular switches.
Dynamic combinatorial chemistry (DCC) methodology utilizes structures which interconvert via reversible covalent bond formation to create a dynamic library of potential receptors. When this thermodynamically controlled mixture is incubated with an analyte, the library responds by shifting the equilibrium towards the receptor that best binds the analyte, i.e. the best receptor is amplified relative to the non-templated state.
We are using DCC to develop selective receptors for biomolecules and post-translational modifications, such as those described above. We are interested in using DCC to explore sequence and structure selectivity and also to develop receptors with signaling capabilities.
