News and Publications

2002 DEPARTMENT HIGHLIGHTS

Kurt Wüthrich, Ph.D., Cecil H. and Ida M. Green Visiting Professor of Structural Biology, shared the 2002 Nobel Prize in Chemistry for the determination of protein structures in solution. This follows close on the heels of another Nobel Prize, the 2001 Nobel Prize in Chemistry, awarded to Skaggs Institute investigator K. Barry Sharpless, Ph.D., who is W.M. Keck Professor of Chemistry.

Numerous other prestigious honors were bestowed on Skaggs Institute faculty, including Professor Albert Eschenmoser, Ph.D., who won the Oparin Medal and the Roger Adams Award in Organic Chemistry; Professor Ian Wilson, D. Phil., who was elected to the American Academy of Arts and Sciences; Director and Professor Julius Rebek, Ph.D., who won the American Institute of Chemists Chemical Pioneer Award; K.C. Nicolaou, Ph.D., (Aline W. and L.S. Skaggs Professor of Chemical Biology and Darlene Shiley Chair in Chemistry) who was selected to receive the Tetrahedron Prize; Chi-Huey Wong, Ph.D., (Ernest W. Hahn Professor and Chair in Chemistry), who was elected to the National Academy of Sciences; and Dale Boger, Ph.D., (Richard and Alice Cramer Professor of Chemistry) who received the Paul Janssen Award for Creativity in Organic Synthesis.

More than 300 publications were generated by Skaggs researchers in the past year.

2002 RESEARCH HIGHLIGHTS

Synthesis lies at the heart of organic chemistry and the synthesis of natural products drives the discoveries of chemical biology. The flow of synthetic molecules from the Skaggs chemistry team at TSRI--Nicolaou, Boger, Associate Professor Erik Sorensen, and Sharpless--has resulted in several remarkably active agents. During the past year antibiotic agents targeting cancer have been the focus of research: duocarmycins that strike at cancerous DNA; designed agents that inhibit growth of blood vessels to tumors; synthetic structures that stabilize microtubules reversibly and those that target proteins and nucleic acids irreversibly. Modified epithilones with reduced toxicity have been synthesized, and an inhibitor of acetyl cholinesterase with unprecedented affinity was created by a process in which the enzyme itself assembles the agent by selecting its components in the active site. The reagents "click" together in the space provided by the enzyme.

The discovery of the group led by TSRI President Richard Lerner, M.D., who is Lita Annenberg Hazen Professor of Immunochemistry and Cecil H. and Ida M. Green Chair in Chemistry, that antibodies are capable of destroying antigens by chemical methods is a profound one and likely to make its greatest impact in future years. It points to the versatility of the immune system and shows that radical new departures can be found in basic science. Current research is directed at identifying which of the activated forms of oxygen, i.e. ozone or hydroxyl radical, is responsible for the chemistry that protects the system from toxic agents.

A discovery that has deep significance for biology emerged from the work of Paul Schimmel, Ph.D., Ernest and Jean Hahn Professor and Chair of Molecular Biology and Chemistry, and Peter Schultz, Ph.D., Professor and Scripps Family Chair, who have been manipulating the genetic code with the aim of engineering living organisms. This has resulted in the discovery of a molecule that inhibits angiogenesis and may also be able to target tumors. This shows such promise that a consortium of scientists were able to obtain long-term support from the National Institutes of Health to pursue the findings.

The group led by Jeffery Kelly, Ph.D., who is Lita Annenberg Hazen Professor of Chemistry, promises to bring a medicinal chemistry effort at TSRI one step closer to clinical trials. This project involves the misfolding of proteins implicated in debilitating diseases such as Alzheimer's and other amyloidoses. The researchers found that a non-steroidal, anti-inflammatory drug approved for other indications prevented this misfolding. The drug is available orally and the results of human clinical studies have been so impressive that it, or a second-generation analog, will be effective in a greater patient population.

A group led by Rebek demonstrated that it could achieve chemical amplification (speeding up a reaction as it proceeds) without the presence of an autocatalyst (a product of the reaction that acts as a catalyst for more product). The findings show a different way of turning a reaction on and off. These findings are important to the study of the dynamics of living systems.