This proposal requests suitable circular dichroism (CD)/magnetic circular dichroism (MCD) equipment to service the long-range objectives of a group of faculty in the Departments of Chemistry and Biochemistry. These faculty are united by a common need for this equipment and by a high level of collegiality. Professors Lightner and Scott are organic chemists who require the instrumentation for long range studies on molecular systems of importance in the phototherapy of jaundice (Lightner) and cancer chemotherapy (Scott). Professor Harrington is a physical biochemist and molecular biologist in the Department of Biochemistry who employs CD and linear dichroism (LD) in a semi-empirical fashion to characterize chromatin structure and structure-function relationships in eukaryotic gene regulation. Lightner and Harrington are also members of the Program in Cellular and Molecular Biology, a new interdisciplinary program recently initiated to link research faculty from several basic science departments at the University of Nevada Reno. The requested facility will be principally used and administered by these three investigators, but will be made available to other competent researchers on a project basis as needed. Immediate goals for the requested facility are as follows. (1) Lightner: Circular dichroism will be used to characterize photoproducts and photoproduct binding of hyperbilirubinemia in infants. Effective chemotherapeuteic agents, especially the metalloporphyrins, are not well understood in their binding nature. CD and MCD are virtually unique in their ability to contribute to these areas. (2) Scott: Useful agents for cancer chemotherapy have been synthesized which offer potential economic large scale production by total synthesis. These compounds, the azuloquinones, require extensive characterization of their electronic structure(s) to permit an effective correlation between structure and cytotoxicity to be made. CD and MCD offer a unique method of approach. (3) Harrington: CD has proved to be a powerful method for characterizing secondary and tertiary structure in the DNA and protein components of chromatin. CD spectra correlated with thermal denaturation methods will include studies of genomic chromatin, specific DNA sequence and cell cycle effects and the role of post-transcriptional histone modifications in the genetic transcription processes. The latter studies will involve the naturally mitotically synchronous cell system, the slime mold Physarum polycephalum.
