Home	Faculty	Research	Graduate Program	Undergraduate Program	Courses	Brookhaven

		Francis Johnson Professor Ph.D., 1954, Glasgow University; Postdoctoral Fellow, Boston University, 1954-57. Joint appointment with Department of Pharmacological Sciences. (631) 632-8866 Email: francis.johnson@sunysb.edu Publications

	ORGANIC CHEMISTRY-MEDICINAL CHEMISTRY The major research interests of this laboratory are concerned with a) chemical aspects of genetic toxicology and b) a program of synthesis aimed at rationally designed drugs to inhibit viral enzymes associated with HIV-1 (AIDS), c) new methods of synthesis involving organo-alkali chemistry. Our approach to studies in genetic toxicology involves the synthesis (automated) of DNA having chemical lesions that arise physiologically from carcinogenic substances or radiation. The chief objective is to examine the mutation spectrum associated with these lesions. This is investigated both by in vitro and in vivo studies with DNA polymerases and repair enzymes. Our work so far has examined lesions associated with acrolein, carcinogenic amines, and oxidation products of both deoxyguanosine and deoxyadenosine, products that are associated with both radiation damage and asbestos-mediated transformations. In the course of this work the oxidation chemistry of the carcinogenic amine adducts has shown that at physiological pH a slow oxygen-induced degradation takes place, producing an array of intermediates derived from the initial adduct. The role of these secondary lesions in carcinogenesis is under investigation. In addition, new protecting groups for the synthesis of DNA containing these lesions have had to be designed to accommodate the extreme sensitivity of a number of these adducts to the normal chemistry of DNA synthesis. In the area of AIDS research, we have been successful in designing new substances that interfere with the reverse transcriptase responsible for the viral DNA/RNA replication. These substances constitute a new class of anti-viral agents in that they inhibit the viral reverse transcriptase at the active site and appear to be irreversible in action. They are active against a range of other viruses, but do not inhibit the cellular DNA synthetases of mammalian cells. The third area of research concerns new synthetic methods. Here, we have discovered a new type of directed ortho-metalation cyclization that allows the easy synthesis of a wide variety of indenediones. Previously, synthetic methods for the preparation of this class of compound were limited to the simplest members of the group. Some of the new compounds are now being tested for anticoagulant and antibiotic activity.

University	Safety	Seminars	Library	Positions Available	Solar System	Molecules	Links