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Organic chemistry and materials science will increasingly revolve around larger and more complex molecules and assemblies that rely on predictable control over non-covalent interactions. The work in our laboratory is inspired by the magnificent macromolecules of nature, especially proteins. The covalent chemistry of proteins is straightforward for the most part, being composed of amide bonds along a repeating backbone. On the other hand, intramolecular and intermolecular non-covalent interactions simultaneously control protein folding and assembly into complex and ultimately functional three-dimensional systems. Our work focuses on the construction of large and complex molecules, and is divided between abiotic designs and recombinant protein engineering. Projects range from basic science studies intended to extend the boundaries of knowledge to applied work geared toward commercial adoption. Synthetic Abiotic Systems Based on Aromatic Electron Donor-Acceptor Interactions The abiotic designs we create center around aromatic electron donor-acceptor interactions that promote face-centered, alternating stacking of electron rich and electron deficient aromatic units. Being driven largely by the hydrophobic effect, this interaction is stronger in polar solvents, making it ideal for folding and assembly of molecules in water. Early work focused on simple folding systems and understanding the interaction as it applies to aqueous solution. More recent projects have developed artificial duplexes, molecules with a novel DNA binding topology analogous to how a snake might climb a ladder, and self-assembling mesophases and polymers.
Molecular Biology Our protein engineering work has been carried out in collaboration with Professor George Georgiou in the College of Engineering at UT Austin. We jointly supervise a laboratory that seeks to develop platform technologies suitable to program new properties and activities into proteins. Out most advanced antibody engineering technology, called APEx, has been licensed to several pharmaceutical companies, and has applications to generalized protein-protein interactions. APEx is a bacteria-based display platform that enables fluorescence activated cell sorting (FACS) isolation of enhanced antibodies, in a process that allows the simultaneous optimization of expression level, antigen affinity, and specificity. We have also developed several approaches to the engineering of enzyme properties, especially antigenicity and substrate specificity. Recent progress in the enzyme area includes the generation of the first family of proteases (enzymes that cleave other proteins) with programmed substrate specificity. Engineered proteases should have a wide variety of important applications including therapeutics. Research Areas
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