Nitric oxide is a cell-signaling molecule involved in a number of physiological and pathophysiological processes. Modification of cysteine residues by nitric oxide, i.e. S- nitrosation, changes the function of a broad spectrum of proteins. This reaction represents an important post-translational modification that transduces nitric oxide- dependent signals. However, the detection and quantification of S-nitrosation in biological samples remains a challenge because of the lability of the S-nitrosation products: S-nitrosothiols (RSNOs). Our group recently developed a series of new reactions for RSNOs, which include bis-ligation, reductive ligation, and reductive elimination (to form dehydroalanine). These reactions selectively target on RSNOs and convert them to stable/detectable products. Based on control experiments, we hypothesize these reactions can be used to design new methods for the detection of RSNOs. In this project, we plan to pursue the following four Specific Aims: (1) to study bis-ligation based methods for detecting protein S-nitrosation;(2) to study reductive ligation based methods for detecting protein S-nitrosation;(3) to study dehydroalanine formation from S-nitrosocysteines and the applications in the detection of protein S- nitrosation;and (4) to validate the applications of new RSNO detection methods in biological systems. These studies will advance the understanding of the chemical and biological properties of RSNOs and permit studies of S-nitrosation-related nitric oxide signal transducation in complex systems.

Public Health Relevance

S-Nitrosation of protein cysteine residues plays important roles in physiology and pathophysiology, while the detection of S-nitrosation is still a challenge. The research proposed here will provide new insights into the chemistry of S-nitrosation and lead to new techniques for the detection of S-nitrosation in biological samples, which should have great impact on biomedical research.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM088226-03
Application #
8325402
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Fabian, Miles
Project Start
2010-09-30
Project End
2015-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
3
Fiscal Year
2012
Total Cost
$291,529
Indirect Cost
$87,414
Name
Washington State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164
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