Recent advances in UV resonance Raman spectroscopy have demonstrated its unique power to examine biomolecular structure and dynamics. The spectra are very sensitive to molecular geometry due to the dependence of the normal mode frequencies on bond lengths and bond angles. The UV Raman spectra detail both static and dynamic structural changes. The information content of UVRR spectroscopy is presently limited by spectrometer throughput, since modern deep UV laser sources provide higher powers than can be utilized for resonance Raman excitation. The excitation intensity threshold is limited by the onset of nonlinear optical processes. We will develop a novel deep UV Raman spectrometer with dramatically improved sensitivity and signal-to-noise ratios to enable incisive investigations of biological structure and function. This spectrometer will be targeted for determining protein and peptide secondary structure and for kinetic studies which examine the dynamics of protein folding. The work proposed here will revolutionize UVRR measurements by developing a new spectrometer which will collect much more Raman scattered light than previous instruments.

Public Health Relevance

Major advances in the understanding of biomolecular structure and function result from the development of more incisive methods to visualize molecular structure and dynamics. An increased understanding of biomolecular structure and function directly leads to insight into human health and is essential for developing methods to treat human disease. The resulting more powerful UV Raman instrumentation will give new insights into the mechanism(s) of protein folding, which is arguably the most important outstanding problem in enzymology. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
1R01EB009089-01
Application #
7565671
Study Section
Instrumentation and Systems Development Study Section (ISD)
Program Officer
Zhang, Yantian
Project Start
2008-09-30
Project End
2012-06-30
Budget Start
2008-09-30
Budget End
2009-06-30
Support Year
1
Fiscal Year
2008
Total Cost
$442,704
Indirect Cost
Name
University of Pittsburgh
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Hong, Zhenmin; Damodaran, Krishnan; Asher, Sanford A (2014) Sodium dodecyl sulfate monomers induce XAO peptide polyproline II to ?-helix transition. J Phys Chem B 118:10565-75
Bykov, Sergei V; Sharma, Bhavya; Asher, Sanford A (2013) High-throughput, high-resolution Echelle deep-UV Raman spectrometer. Appl Spectrosc 67:873-83
Ma, Lu; Sikirzhytski, Vitali; Hong, Zhenmin et al. (2013) Insight into resolution enhancement in generalized two-dimensional correlation spectroscopy. Appl Spectrosc 67:283-90
Hong, Zhenmin; Wert, Jonathan; Asher, Sanford A (2013) UV resonance Raman and DFT studies of arginine side chains in peptides: insights into arginine hydration. J Phys Chem B 117:7145-56
Oladepo, Sulayman A; Xiong, Kan; Hong, Zhenmin et al. (2012) UV resonance Raman investigations of peptide and protein structure and dynamics. Chem Rev 112:2604-28
Xiong, Kan; Ma, Lu; Asher, Sanford A (2012) Conformation of poly-L-glutamate is independent of ionic strength. Biophys Chem 162:1-5
Xiong, Kan; Asher, Sanford A (2012) Impact of ion binding on poly-L-lysine (un)folding energy landscape and kinetics. J Phys Chem B 116:7102-12
Xiong, Kan; Punihaole, David; Asher, Sanford A (2012) UV resonance Raman spectroscopy monitors polyglutamine backbone and side chain hydrogen bonding and fibrillization. Biochemistry 51:5822-30
Wang, Luling; Tikhonov, Alexander; Asher, Sanford A (2012) Silica crystalline colloidal array deep ultraviolet narrow-band diffraction devices. Appl Spectrosc 66:426-31
Ma, Lu; Hong, Zhenmin; Sharma, Bhavya et al. (2012) UV resonance Raman studies of the NaClO4 dependence of poly-L-lysine conformation and hydrogen exchange kinetics. J Phys Chem B 116:1134-42

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