Natural and Man-made Therapies from the Laboratory Joseph Konopelski, Chemistry and Biochemistry Numerous drugs and reagents used in biomedical research originate from products derived from plant and animal life. In the laboratory of Joseph Konopelski, investigators synthesize variant forms of these molecules for biomedical research. Keywords: Organic Synthesis, Synthetic Methodology, Asymmetric Synthesis, Heterocycles, Bioorganic Chemistry, Protein Chemistry and Synthesis, Biochemistry (Keywords: Natural Products, Organic Synthesis, Synthetic Methodology, Asymmetric Synthesis, Heterocycles, Bioorganic Chemistry, Cancer, Protein Chemistry and Synthesis)

Natural Products Have Long Been Utilized as a Source for Drugs

Natural products derived from terrestrial sources have been employed as medicinal agents since the dawn of history. During the past seventy-five years, Western medicine has explored purified compounds derived from these sources with great interest and intensity. More recently, marine sources have also begun to yield many novel natural products with exciting biological activity. It is estimated that approximately 70% of anti-microbial and anti-cancer drugs currently approved for human use originate from natural products. Moreover, 30% of the best-selling small molecule drugs in 1999 were either derived from or developed through a study of natural products.

The structures of these natural compounds are extraordinarily unique, since they arise from millions of years of evolutionary pressure. These materials are often used directly. For example, taxol and bleomycin serve as anti-tumor agents. In other cases, synthetic organic chemists effect some modification of the natural product so that the new compound is sufficiently active and selective for human use.

Researchers Also Exploit Natural Chemical Structures to Examine Cellular Processes

These novel chemical structures not only serve as the basis for new chemotherapeutic agents, they also become key elements in the discovery and analysis of cellular processes. For example, phalloidin, which is derived from the poisonous mushroom, Amanita phalloides, can be fluorescently labeled and is widely used to examine the role of the protein actin in muscle, the cytoskeleton, and the cell cycle.

Knowledge of the cellular responses to a given biologically active compound allows researchers to "map" the interactions of cellular components over time and stress. In the process, new cellular pathways are defined, which in turn allow for the development of more effective chemotherapeutic agents.

Searching for Specific Compounds Used in Biological Evaluation

Research efforts in the Konopelski laboratory are shaped by the demand for useful quantities of natural products and specifically designed synthetic materials for biological evaluation. Rational design and execution of a multistep synthesis remains one of the most challenging areas of chemistry. It requires not only a ready knowledge of organic transformations and sophisticated laboratory technique, but also a fundamental understanding of many other areas of chemistry, ranging from modern theory and reaction mechanism to organometallic chemistry. In many cases, particularly with regard to marine natural products, the desired active compound is available in minute quantities too small for complete evaluation. Thus, it becomes important to develop a "blueprint" of synthetic organic reactions that, when performed in the correct sequence, produces the desired natural material in suitable quantity for evaluation. Equally important is the need to obtain modified versions of the natural product structure in order to evaluate the required structural elements for bioactivity.