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A4644 - Naphathalene-Based Fluorescent Probes for Glutathione and Their Applications in Living Cells and Patients with Sepsis
Author Block: B. Kim1, J. Yoon2, J. Ryu3; 11.Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea., Seoul, Korea, Republic of, 22.Department of Chemistry and Nano Science, Ewha Womans University, Seoul 120-750, Korea, Seoul, Korea, Republic of, 31.Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea, Seoul, Korea, Republic of.
Biothiols, specifically glutathione (GSH), play important roles in biological systems and physiological processes. Abnormal levels of GSH are related to many diseases, such as sepsis, liver damage, cancer and etc. Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and results in severe oxidative stress and damage to multiple organs. Patients with sepsis have low plasma GSH peroxidase activity and low GSH levels. So, although redox therapy in sepsis has rarely been successful in human clinical trials, the measurement of GSH levels has clinical relevance. We hypothesized that GSH and Hcy/Cys react with an o-dialdehyde group in different modes which would exhibit different fluorescence signal responses; and by introducing different functional groups on naphthalene ring (i.e., -H, -OCH3 and -F), the probes may display different sensing abilities towards biothiols. On the basis of this hypothesis, we develop a highly selective and sensitive fluorescent probe for GSH, two new naphthalene dialdehyde compounds. These compounds contain different functional groups which were synthesized. To confirm these compounds, we checked some points such as synthesis of NDA derivatives, UV and fluorescence properties of GSH Probes, sensing mechanism of NDA and its derivatives, one photon imaging of probes with GSH, two photon imaging of MDNA with GSH, and finally application of GSH probes in serum. Consequently, Our study found that the newly developed probe 6-methoxynaphtalene-2, 3-dicarbaldehyde (MNDA) which incorporates an electron-donating group, can simultaneously detect GSH and Hcy in different signal channels and this probe is capable of detecting GSH in live cells with two-photon microscopy (TPM) under the excitation at a wavelength of 900 nm. Moreover, two GSH detection probes NDA and FNDA can detect GSH in living cells. And also NDA and FNDA were able to detect GSH level in the plasma of patients who suffered from sepsis. It means that NDA and FNDA have a clinical significance for the diagnosis and prediction of mortality in patients with sepsis. So, we believe these results open up a promising direction for further medical diagnostic techniques.