The amino-acid sequences of proteins encode their three-dimensional structures, and these structures engender life. Using techniques that range from synthetic chemistry to cell biology, we are illuminating in atomic detail both the chemical basis and the biological purpose for protein structure and protein function. Our efforts are leading to insights into the relationship between amino-acid sequence and protein function (or dysfunction), as well as to the creation of novel proteins with desirable properties. We are now focused on the following problems.
Proteins produced by recombinant DNA technology are limited to twenty or so alpha-amino acids. We have developed a new chemical reaction-the traceless Staudinger ligation-as a means to assemble synthetic peptides into proteins and thereby escape from the tyranny of the genetic code. We are also seeking to use other chemoselective reactions in biological contexts, such as this gentle means to convert an azide into a carbene:
Nearly ¼ of human proteins contain disulfide bonds, which are formed by the oxidation of the sulfhydryl groups of cysteine residues. We are creating new organocatalysts for this important, and often problematic, process.
We have discovered that stereoelectronic effects stabilize folded proteins. By exploiting this effect, we have synthesized simple derivatives of collagen that are far more stable than any natural collagen. We have also used molecular self-assembly to produce collagen triple helices that are far longer than any natural one. These discoveries are spawning new materials for biomedicine and nanotechnology.
By catalyzing the cleavage of RNA, ribonucleases can be cytotoxic. Most notably, a human ribonuclease variant discovered by our group is now in clinical trials as a cancer chemotherapeutic agent. We are using both chemical and biological tools to reveal the mechanism by which this remarkable toxin kills cancer cells specifically.
Green Chemistry and Biofuels
We are developing chemical processes to convert crude lignocellulosic biomass (such as corn stover and pine sawdust) into useful fuels and chemicals. In particular, we are exploring and exploiting this reaction scheme, which we can effect in one step with nearly 50% yield:
Our research projects are designed to reveal how biological phenomena can be explained and manipulated by using chemical principles. Our hypotheses are far-reaching, and testing them requires the use of techniques and ideas from diverse disciplines. This broad/deep training is appropriate for scientists who want to perform innovative and meaningful research at the widening chemistry-biology interface.