Ronald T. Raines

Professor of Chemistry and Biochemistry, Born 1958
Sc.B. 1980, Massachusetts Institute of Technology
A.M. 1982, Harvard University
Ph.D. 1986, Harvard University

Room: 371 BC
Phone: 608-262-8588
Email: rtraines@wisc.edu
Position: Professor

Research Description

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.

Protein Chemistry. 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:

Protein Folding. 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.

Protein Stability. 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.

Protein Function. 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.

Publications

• Choudhary, A.; Gandla, D.; Krow, G. R.; Raines, R. T. Nature of amide carbonyl - carbonyl interactions in proteins. J. Am. Chem. Soc. 2009, 131, 7244.

• Dickson, K. A.; Raines, R. T. Silencing an inhibitor unleashes a cytotoxic enzyme. Biochemistry 2009, 48, 5051.

• Shoulders, M. D.; Kamer, K. J.; Raines, R. T. Origin of the stability conferred upon collagen by fluorination. Bioorg. Med. Chem. Lett. 2009, 19, xxx.

• Dickson, K. A.; Kang, D.-K.; Kwon, Y. S.; Kim, J. C.; Leland, P. A.; Kim, B.-M.; Chang, S.-I.; Raines, R. T. Ribonuclease inhibitor regulates neovascularization by human angiogenin. Biochemistry 2009, 48, 3804.

• Myers, E. L.; Raines, R. T. A phosphine-mediated conversion of azides to diazo compounds. Angew. Chem. Int. Ed. 2009, 48, 2359.

• Binder, J. B.; Raines, R T. Simple chemical transformation of lignocellulosic biomass into furanics for fuels and chemicals. J. Am. Chem. Soc. 2009, 131, 1979.

• Tam, A.; Raines, R. T. Coulombic effects on the traceless Staudinger ligation in water. Bioorg. Med. Chem. 2009, 17, 1055.

• Yatzeck, M. M.; Lavis, L. D.; Chao, T.-Y.; Chandran, S. S.; Raines, R. T. A highly sensitive fluorogenic probe for cytochrome P450 activity in live cells. Bioorg. Med. Chem. Lett. 2008, 18, 5864.

• Kalia, J.; Raines, R. T. Hydrolytic stability of hydrazones and oximes. Angew. Chem. Int. Ed. 2008, 47, 7523.

• Gorres, K. L.; Edupuganti, R.; Krow, G. R.; Raines, R. T. Conformational preferences of substrates for human prolyl 4-hydroxylase. Biochemistry 2008, 47, 9447.

Awards

• Kellett Mid-Career Faculty Researcher Award, University of Wisconsin-Madison, 2009-2014

• Technology Achievement Award, MIT Club of Wisconsin, 2007

• Rao Makineni Lectureship Award, American Peptide Society, 2007

• Fellow, Royal Society of Chemistry, 2006

• Emil Thomas Kaiser Award, Protein Society, 2005

• Arthur C. Cope Scholar Award, American Chemical Society, 2004

• Vilas Associates Award, University of Wisconsin-Madison, 2002-2004

• H. I. Romnes Faculty Fellowship, University of Wisconsin-Madison, 1998-2003

• Fellow, American Association for the Advancement of Sciences, 2002

• Guggenheim Fellowship, J. S. Guggenheim Memorial Foundation, 2001-2002