9318233 Sweeney This Proposal requests instrumentation to permit the assembly of a prototype of a new spectrometer, employing vibrational circular dichroism (VCD); the optics will incorporate a step-scanning interferometer, based on a Fourier transform methodology. The spectrometer will be the first of its kind and will be capable of increasing the sensitivity of VCD measurements by 2 to 3 orders of magnitude. A unique feature of such an instrument will be its ability to detect solution structures with lifetimes in the nanosecond range -- structures normally invisible in NMR analysis. This will make it applicable to a broad range of structure problems involving biological macromolecules. One of the major users, Dr. Max Diem, has extensive experience in VCD, having designed and built his own instrument with the help of NSF grant funds several years ago. This instrument is currently being used for polypeptide and polynucleotide structural studies in the Chemistry Department, but its sensitivity limits its use to molecules in the range of one kilo-Dalton. Various projects are described, from laboratories at Hunter and at New York University, which include investigations of basic aspects of protein and nucleic acid structures in solution, structures of metalloproteins, and facets of the initiation complex in protein synthesis, as well as drug-DNA interactions, and the design of metal-complexed chemotherapeutic agents. It is anticipated that the new instrument will attract additional users from the Sloan-Kettering Institute for Cancer Research, the Rockefeller University and other institutions in New York City.
