A team of NIH-funded investigators request funds to purchase a circular dichroism (CD) spectrometer. The instrument will be used to gain comprehensive understanding of a broad range of molecules, including secondary structure of proteins and natural and synthetic peptides, transition metal-nucleotide catalysts, and bioactive small molecules. It will also be used for developing enantioselective reactions of natural and unnatural small molecules of medical significance. Specific examples of how the CD spectrometer will be used include: screening structural differences in mutant transporter protein libraries that are related to genetic diseases, investigating the role of temperature on the structure of methyltransferases, examining how posttranslational modifications affect the structure of translation elongation factor(s), analyzing chain conformations in synthetic and polypeptides, nucleotide polymers, and probing enantioselective reactions to design and develop natural and unnatural small molecules that are of medical and biological significance. The current CD spectrometer housed in the UCLA-DOE Biochemistry Instrumentation facility is one of only two instruments at UCLA, and the only one found in a core facility that accepts a large user base. However, it is over 20 years old and parts are no longer available to maintain the level of performance required. Therefore, access to this technology is currently lacking to the general research community at UCLA. The specific instrument we are requesting is a Chirascan V100 spectrometer (standard with a high sensitivity solid state absorbance/CD detector, avalanche photodiode, and water circulator for heat dissipation from sample storage Peltier) manufactured by Applied Photophysics. The Chirascan V100 represents the state-of-the-art in CD spectrometer technology. It exhibits exceptional sensitivity, speed, and robustness for circular dichroism experiments. Thus, it is well suited to serve the needs of the UCLA research community. The spectrometer will be located in the UCLA-DOE Biochemistry Instrumentation Facility where it will be accessible to the entire UCLA research community. Two highly experienced Ph.D.-level staff members with full salary support from UCLA, will be responsible for the maintenance, operation, and training of individuals on the instrument. Additionally, UCLA will provide funds to support the service contract for the spectrometer to ensure it is properly maintained and calibrated for long-term use by the broader research community at UCLA.
Biological activities of proteins and small molecules depend on their structures and chirality. Instruments that determine chirality of small molecules, secondary structure, and conformational changes of proteins are crucial to understanding how these molecules function. This grant application requests funds to purchase a new circular dichroism spectrometer, which can be used to study the chirality and structure of both small molecules and proteins.
