Thirteen faculty members (including seven NIH-supported major users) from UC Santa Cruz, and CSU San Francisco, CSU San Jose, and Duke University request funds to purchase a new circular dichroism (CD) spectrometer. Our existing departmental CD instrument is over 20 years old, frequently needs repairs, and is no longer supported by the vendor. The requested JASCO J-815 CD includes an automated titrator, a stopped-flow attachment, and a magnet for magnetic CD (MCD) studies, capabilities of great value to many of the project faculty. It will not only allow the continuation of research discussed below, but also enhance our biomedical research capability by providing the best state-of-the-art performance specifications on the market. It will automate denaturant titration studies, increasing research pace, improve sensitivity of MCD data, and make possible time-resolved structural studies. Such currently unavailable investigative paths are vital for ongoing projects. CD has long played a critical role in research at UCSC. Research of the seven major users can be divided into four areas: 1) protein/DNA structure and functional investigations, 2) protein folding kinetic mechanisms, 3) stereochemical structure elucidation, and 4) determination of fundamental mechanisms in biologically significant systems. Two major and one minor user in Area 1 will use the spectrophotometer to determine protein and DNA structure and stability and to characterize structure and function of peptides for HIV vaccine development. In Area 2, one major and one minor user will employ CD to characterize protein structure and stability and monitor protein folding kinetics at times longer than tens of milliseconds. One major and one minor user in Area 3 will employ CD to obtain chiroptical data for structural elucidation of bioactive marine-derived natural products that are potent against disease, and for development of chiral structural probes to study enantiomeric recognition of biological substrates. CD will be used by three major and two minor users in Area 4 to characterize protein structure and mechanisms in biochemical processes (light-dependent energy conversion and signal transduction, metal binding in neuron maintenance and neuronal disease, coupled electron transfer and proton translocation, cell cycle, circadian rhythm). One minor user will use CD to investigate the reaction of intermediates involved in nitric oxide synthase catalysis (Area 4), as well as the structure and stability of monomeric and dimeric histones (Area 1). Biomedical research is a priority at UCSC, which continues to expand its faculty and research facilities. A Physical Sciences Building, completed in 2006, provides 79,800 asf of space for the Depts. of Chemistry and Biochemistry and Environmental Toxicology, and a Biomedical Sciences Building was opened in 2012. This new infrastructure will facilitate a large increase in biomedical research over the next decade. Our NIH-funded faculty have used UCSC's current CD to advance research areas of pressing biomedical need. However, we must replace our aging instrumentation, so the proposed CD instrument is vital to the continued advancement of our researchers.
|Warner, Christopher J A; Dutta, Subrata; Foley, Alejandro R et al. (2017) Using chiral peptide substitutions to probe the structure function relationship of a key residue of A?42. Chirality 29:5-9|
|Dutta, Subrata; Foley, Alejandro R; Warner, Christopher J A et al. (2017) Suppression of Oligomer Formation and Formation of Non-Toxic Fibrils upon Addition of Mirror-Image A?42 to the Natural l-Enantiomer. Angew Chem Int Ed Engl 56:11506-11510|
|Warner, Christopher J A; Dutta, Subrata; Foley, Alejandro R et al. (2016) Introduction of d-Glutamate at a Critical Residue of A?42 Stabilizes a Prefibrillary Aggregate with Enhanced Toxicity. Chemistry 22:11967-70|