News and Publications

2002 DEPARTMENT HIGHLIGHTS

Chair K.C. Nicolaou, Ph.D., who is Aline W. and L.S. Skaggs Professor of Chemical Biology and Darlene Shiley Chair in Chemistry, was the 2002 winner of the Nobel Laureate Signature Award, with Phil Baran, a 2002 graduate of the TSRI Chemistry Program. Nicolaou also won the Tetrahedron Prize for Creativity in Organic Chemistry.

Professor Albert Eschenmoser, Ph.D., won the Roger Adams Award in Organic Chemistry given for "outstanding contributions to research in organic chemistry defined in its broadest sense." Eschenmoser also received the Oparin Medal, the highest recognition of the International Society for the Study of the Origin of Life.

Chi-Huey Wong, Ph.D., Ernest W. Hahn Professor and Chair in Chemistry, was elected a member of the National Academy of Sciences.

Dale Boger, Ph.D., Richard and Alice Cramer Professor of Chemistry, received the 2002 Paul Janssen Prize for Creativity in Organic Synthesis.

Peter Schultz, Ph.D., professor and Scripps Family Chair, won the Paul Ehrlich & Ludwig Darmstaedter Award.

Nicolaou, Wong, K. Barry Sharpless, Ph.D., (who is W.M. Keck Professor of Chemistry), Boger, and Julius Rebek, Ph.D., (who is professor and director of The Skaggs Institute for Chemical Biology) were included in the Institute of Scientific Information's list of "100 Most-Cited Researchers in Chemistry" for the period January 1992 through June 2002.

2002 RESEARCH HIGHLIGHTS

Boger disclosed the first total synthesis of ramoplanin--a complex antibiotic. Ramoplanin inhibits cell wall biosynthesis in bacteria and is active against emerging antibiotic-resistant bacterial infections.

Associate Professor M.G. Finn, Ph.D., published the first reports of the use of icosahedral virus particles as building blocks for organic chemistry (with Professor J. Johnson, Ph.D., Department of Molecular Biology). This work provides a bridge between the worlds of chemistry, which features known, but relatively small molecular structures, and biology, which features large entities of uncertain structure.

Professor Kim Janda, Ph.D., Ely R. Callaway, Jr., Chair in Chemistry, discovered that nornicotine, a nicotine metabolite and constituent of tobacco, can catalyze chemical reactions as well as modify proteins in vivo, implicating nornicotine in diabetes, cancer, aging, and arteriosclerosis.

Janda prepared the first human antibodies raised against Bacillus spores, in a species similar to that which causes anthrax. The study demonstrated spore detection and may lead to a new treatment for victims of anthrax.

Janda also showed that immunization with a synthetic glycoconjugate leads to up to 94 percent protection against septic shock, the tenth-leading cause of death in the United States today.

Nicolaou synthesized Diazonamide A, a marine-derived natural product with potent antitumor activity. This feat provides a potential lead to new anticancer agents.

Assistant Professor Floyd Romesberg, Ph.D., and his group, in collaboration with the Shultz group, developed several unnatural base pairs that are stable and replicated by polymerase enzymes. This is part of a broader effort to expand the information potential of DNA. Such unnatural bases pairs could, in principal, be used to expand an organism's genetic alphabet and encode proteins not found in nature.

The Romesberg group also recently developed a spectroscopic method to quantitatively characterize protein flexibility and folding. The lab is using this approach to understand molecular recognition in the immune system.

Using high-throughput screens, the group identified six novel proteins that function to maintain genome stability. The same techniques are being used to identify proteins required for cell mutation.

Sharpless, in collaboration with Finn, discovered an extremely potent non-covalent inhibitor of acetylcholinesterase using his "click chemistry" approach, where the enzyme itself recruits the building blocks and synthesizes the inhibitor in its active site.

Sharpless also discovered the copper(I)-catalyzed ligation of azides and terminal alkynes, one of the most selective and efficient catalytic processes known to date.

The laboratory of Associate Professor Erik Sorensen, Ph.D., achieved gram-scale laboratory syntheses of the structurally complex and potent microtubule-stabilizing natural product (­)-FR182877 and its enantiomer. This research led to the first report of tandem transannular Diels-Alder reactions and provided a chemical rationalization of the complex hexacyclic architecture of FR182877, a potent antitumor agent.

Wong developed saccharide microarrays in microtiter plates for high-throughput screen of saccharides and aminoglycosides targeting proteins and RNA associated with diseases. Wong elucidated the mechanism of a sulfotransferase and discovered a potent and highly selective inhibitor. Sulfotransferases are involved in viral entry to hosts, cancer metastasis, thrombosis, and inflammatory reactions and are new targets for drug discovery.