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1 May 2002 Properties of Selected S-Nitrosothiols Compared to Nitrosylated WR-1065
William Michael Whiteside, Devin N. Sears, Paul R. Young, David B. Rubin
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Abstract

Whiteside, W. M., Sears, D. N., Young, P. R. and Rubin, D. B. Properties of Selected S-Nitrosothiols Compared to Nitrosylated WR-1065. Radiat. Res. 157, 578–588 (2002).

WR-1065 ([N-mercaptoethyl]-1–3-diaminopropane), the active form of the aminothiol drug Ethyol®/Amifostine®, protects against toxicity caused by radiation, chemotherapy and endotoxin. Because WR-1065 and other thiols readily bind nitric oxide (NO), injurious conditions or therapies that induce the production or mobilization of NO could alter the effects of WR-1065. S-Nitrosothiols were prepared from various thiols by a standard method to compare properties and stability. Heteromolecular quantum correlation 2D nuclear magnetic resonance was used to characterize nitrosylated glutathione (GSH) and WR-1065; both S- and N-nitrosothiols were observed, depending on the experimental conditions. Three categories of S-nitrosothiol stability were observed: (1) highly stable, with t1/2 > 8 h, N-acetyl-l-cysteine nitrosothiol (t1/2 15 h) > GSH nitrosothiol (t1/2 8 h); (2) intermediate stability, t1/2 ∼ 2 h, cysteamine nitrosothiol and WR-1065 nitrosothiol; and (3) low stability, t1/2 < 1 h, cysteine nitrosothiol and Captopril nitrosothiol. Similar relative rates were observed for Hg 2-induced denitrosylation: WR-1065 reacted faster than GSH nitrosothiol, while GSH nitrosothiol reacted faster than N-acetyl-l-cysteine nitrosothiol. Mostly mediated by mixed-NPSH disulfide formation, the activity of the redox-sensitive cysteine protease, cathepsin H, was inhibited by the S-nitrosothiols, with WR-1065 nitrosothiol > cysteine nitrosothiol > N-acetyl-l-cysteine nitrosothiol and GSH nitrosothiol. These observations indicate that, relative to other nitrosylated non-protein thiols, the S-nitrosothiol of WR-1065 is an unstable non-protein S-nitrosothiols with a high reactive potential in the modification of protein thiols.

William Michael Whiteside, Devin N. Sears, Paul R. Young, and David B. Rubin "Properties of Selected S-Nitrosothiols Compared to Nitrosylated WR-1065," Radiation Research 157(5), 578-588, (1 May 2002). https://doi.org/10.1667/0033-7587(2002)157[0578:POSSNC]2.0.CO;2
Received: 19 April 2001; Accepted: 1 November 2001; Published: 1 May 2002
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