News and Publications

Year In Review - 2000

Chemistry

K.C. Nicolaou, Ph.D., Chairman

esearchers in the Department of Chemistry conduct scientific inquiries at the frontiers of chemical synthesis, combinatorial chemistry and chemical biology. These disciplines are crucial to understanding human biology and comprise critical new components of modern drug discovery and development. The approximately fifteen faculty members in the department are distinguished teacher-scholars engaged in a broad spectrum of independent research programs in areas as diverse as biological and chemical catalysis, natural products synthesis, molecular design, chemical evolution, materials science, and chemical biology.

Working at the interface of chemistry and biology, faculty members continue to collaborate extensively with biologists and clinicians to uncover the mysteries of a range of biological processes and combat human disease. Through these interdisciplinary research programs, the power of chemistry is brought to bear on numerous biological problems that may one day lead to biomedical breakthroughs and create new, and much needed,medicines and therapeutics.

Faculty members target architecturally novel and biologically-active natural products for total synthesis to discover and invent new synthetic technologies that may help facilitate further biomedical research, and for their relevance to future medical treatments. In their search for these molecules, researchers are often challenged to develop novel synthetic strategies and create new synthetic technologies. At the same time, they take advantage of the opportunity to design and synthesize analogs of naturally occurring substances in the hope that they might have superior pharmacological profiles. As a result of these related efforts, scientists in the department have synthesized a number of such natural and designed molecules and discovered several with promising pharmacological profiles. Currently, several new projects are directed toward the chemical synthesis of antitumor, antibiotic and antiviral agents, and other molecules with health-modulating properties.

A number of faculty members and their research groups are engaged in combinatorial chemistry, a process that has revolutionized the drug discovery process, and promises to have a major impact on biology and medicine in the future. Combinatorial chemistry involves the synthetic assembly of novel molecules in various combinations to produce large libraries of thousands -- often millions -- of compounds for drug screening purposes or specific chemical properties. The screening of these libraries of compounds against specific biological targets often leads to the discovery of new tools or compounds that can, once their molecular structures are refined, become leading drug candidates. From such programs, several enabling technologies for biology and medicine have been developed, and a number of promising compounds that regulate important biochemical pathways have been discovered.

The basic principles of combinatorial chemistry have their origins in nature, where random mutations often lead to vast numbers of biomolecules that undergo subsequent selection and evolution. Mimicking such practices, a number of laboratory groups in the department have devised new protocols for the generation and selection of useful biomolecules such as catalytic antibodies and nucleic acids that facilitate important chemical reactions. Together with other catalytic systems developed in the department--both naturally occurring and synthetic--these catalysts are being used to accelerate certain chemical processes and facilitate new biomedical applications.

Cutting-edge molecular recognition studies are part of the department's ongoing activity that may help provide fundamental insights into the ligand-biomolecule interactions. Such endeavors, aside from their unique artistic appeal, are helping delineate basic molecular architectures and require precise molecular design and sophisticated chemical synthesis techniques. As a result, they often lead to a far greater understanding of molecular assembly processes that may facilitate the design of potential drug candidates. Department researchers are developing designs for enzyme inhibitors, important agents that can block the underlying mechanisms of certain diseases. Several promising compounds of this type have been identified through chemical and enzymatic synthesis followed by biological screening.

In addition to the diverse studies on the large biomolecules such as proteins, DNA, RNA, and polysaccharides, a number of laboratories are focused on research aimed at understanding small segments of these superstructures, namely peptides, oligonucleotides, and oligosaccharides and small organic ligands. The potential benefit of this work includes new antibiotics, antiviral agents, and treatments for diseases such as Alzheimer's, cancer and AIDS. Chemistry relating to the possible origins of life on earth using such designed molecules is also being explored.

With the sequencing of the human genome nearly complete, chemistry is poised to make decisive contributions in the search for new medicines to treat modern disease. While the discipline will be crucial in the development of the evolving field of proteomics (the identification and understanding of the function of the body's protein network), chemists face the challenge of designing and synthesizing the millions of molecules needed to select those ligands that can regulate disease-relevant biological targets with far better outcomes. With its talented and motivated faculty and students, the Depart-ment of Chemistry is well positioned to capitalize on the new genetic information available, and exploit the enormous opportunities that lie ahead.