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Media type:
E-Article
Title:
First insights into regiospecific transnitrosation reactions between tryptophan derivatives: melatonin as an effective target
Contributor:
Kirsch, Michael;
De Groot, Herbert
Published:
Wiley, 2005
Published in:
Journal of Pineal Research, 38 (2005) 4, Seite 247-253
Language:
English
DOI:
10.1111/j.1600-079x.2004.00200.x
ISSN:
0742-3098;
1600-079X
Origination:
Footnote:
Description:
Abstract: Melatonin, a derivative of the essential amino acid tryptophan, has been portrayed as a hormone, a tissue factor, an autocoid, a paracoid, and a vitamin with antioxidative capabilities. In the present study a novel reaction which cannot be attributed to any of these suggested features, i.e. the transfer of the nitroso‐function from N‐nitrosotryptophan derivatives to melatonin, is unequivocally demonstrated. In the lipophilic buffer dimethylsulfoxide reaction of N‐acetyl‐N‐nitrosotryptophan (NANT) with melatonin was very slow (k = 1.5 × 10−6/m/s), but reversible as shown by 15N‐NMR spectrometry. These measurements demonstrated also that the thermodynamical equilibrium lies on the side of N‐nitrosomelatonin (NOMela). Quantum‐chemical calculations performed with the third‐generation density functional B97‐2 additionally predicted that this is also the case in an aqueous environment. In fact, reaction of melatonin with either NANT or N‐nitrosotryptophan located at the endothelin‐1 fragment 16–21 yielded NOMela with a rate constant of 1.7 ± 0.5/m/s as shown by capillary zone electrophoresis. Interestingly, the known reactive nitrogen oxide species scavenger, piperazine, did not inhibit the NANT‐dependent nitrosation of melatonin, thus very strongly indicating a direct transnitrosation reaction. All of these capabilities are known from the reaction of S‐nitrosothiols with thiolate anions and are believed to be highly important in the transport and targeting of nitric oxide.