The design of new catalysts from basic principles of reactivity provides critical tests of how well we understand biocatalysis. We are interested in the introduction of catalytic sites into folded four-helix bundle proteins where amino acid side chains cooperatively catalyze a variety of hydrolytic and acyltransfer reactions
New structures and folds
We have shown that the conjugation of a small organic molecule to the side chain of an amino acid on the accessible surface of a poorly folded polypeptide can transform it into a compact protein molecule with increased stability in a one-step reaction. We have an interest in fast routes to functional proteins with increased stabilities for applications in biotechnology.
The molecular recognition of proteins in vitro and in vivo
We have developed a unique technology for protein recognition based on the conjugation of small organic molecules or short peptides to polypeptides from a designed set. The conjugate molecules bind proteins with high affinities, and with selectivities that are equal to those of antibodies. Conjugation to the polypeptides results in molecules with as much as four orders of magnitude higher affinities than the small molecule or peptide and increased selectivities. We develop binders for a variety of proteins of biomedicinal interest.
Medicinal chemistry and medical imaging
We have developed several binder molecules for specific proteins of interest in the clinic, for diagnostic applications and drug development. We have an interest in using positron emission tomography or PET to trace the fate of molecules in animal models or in humans and to develop new molecular concepts that increase bioavailability and selectivity as well as reduce the toxicity of drugs.