This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Melanin is a key component of the human pigmentary system. The degree of pigmentation of the human skin, eyes or hair is to a large extent determined by the ability of cells to synthesize eumelanin and pheomelanin. The various functions of the melanins are defined by their chemical and physical properties. These properties in turn are defined by the molecular, supermolecular and aggregate-level structures. The ultimate goal is to construct a consistent model of these physical effects in order to engender understanding of how molecular and cellular scale structures relate to macroscopically observable properties and functions of melanins aiding the design of appropriate medical treatment modalities. Most natural melanin pigments exhibit a single, slightly asymmetric ESR signal at X-band that contains very little structural information. Preliminary W-band cw-ESR measurements of natural melanin granules, isolated from human retinal pigment epithelium, indicate distinct changes of the ESR spectrum that suggest possible age-dependent in situ photo oxidation of the ocular melanin.
Our aim i s to use even higher ESR frequencies/fields to spectrally resolve these small physicochemical changes of ocular melanin that may result from integrated exposure to light and oxidative stress. Our initial cw study is at 170/240 GHz concentrated on synthetic melanin (Sigma Aldrich). Notably, the major spectral features are very similar to that of humic acid. We found that the spectrum of the sodium salt of humic acid (Sigma-Aldrich) at 241 GHz/9T has to within experimental uncertainty the same linewidth and g-factor as observed for synthetic melanin. The interesting question is the origin of the subtle, narrow features contained in the broad single line of the synthetic melanin. Since melanins are known for their unusual electric conductivity behavior, it is possible that the presence of the narrow line in the spectrum of synthetic melanin demonstrates correlations between semiquinone radicals (abundant in melanin). Further multifrequency HFHF ESR, due to its superior g-factor resolution, and pulse ESR investigation will help to distinguish and separate between the two broad and narrow components of the spectrum and refine their interpretation.
|Pratt, Ashley J; Shin, David S; Merz, Gregory E et al. (2014) Aggregation propensities of superoxide dismutase G93 hotspot mutants mirror ALS clinical phenotypes. Proc Natl Acad Sci U S A 111:E4568-76|
|Georgieva, Elka R; Borbat, Peter P; Ginter, Christopher et al. (2013) Conformational ensemble of the sodium-coupled aspartate transporter. Nat Struct Mol Biol 20:215-21|
|Airola, Michael V; Huh, Doowon; Sukomon, Nattakan et al. (2013) Architecture of the soluble receptor Aer2 indicates an in-line mechanism for PAS and HAMP domain signaling. J Mol Biol 425:886-901|
|Airola, Michael V; Sukomon, Nattakan; Samanta, Dipanjan et al. (2013) HAMP domain conformers that propagate opposite signals in bacterial chemoreceptors. PLoS Biol 11:e1001479|
|Sun, Yan; Zhang, Ziwei; Grigoryants, Vladimir M et al. (2012) The internal dynamics of mini c TAR DNA probed by electron paramagnetic resonance of nitroxide spin-labels at the lower stem, the loop, and the bulge. Biochemistry 51:8530-41|
|Yu, Renyuan Pony; Darmon, Jonathan M; Hoyt, Jordan M et al. (2012) High-Activity Iron Catalysts for the Hydrogenation of Hindered, Unfunctionalized Alkenes. ACS Catal 2:1760-1764|
|Dzikovski, Boris; Tipikin, Dmitriy; Freed, Jack (2012) Conformational distributions and hydrogen bonding in gel and frozen lipid bilayers: a high frequency spin-label ESR study. J Phys Chem B 116:6694-706|
|Gaffney, Betty J; Bradshaw, Miles D; Frausto, Stephen D et al. (2012) Locating a lipid at the portal to the lipoxygenase active site. Biophys J 103:2134-44|
|Maeda, Kiminori; Lodge, Matthew T J; Harmer, Jeffrey et al. (2012) Electron tunneling in lithium-ammonia solutions probed by frequency-dependent electron spin relaxation studies. J Am Chem Soc 134:9209-18|
|Georgieva, Elka R; Roy, Aritro S; Grigoryants, Vladimir M et al. (2012) Effect of freezing conditions on distances and their distributions derived from Double Electron Electron Resonance (DEER): a study of doubly-spin-labeled T4 lysozyme. J Magn Reson 216:69-77|
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