Ring-Opening Photoreactions of 5-Methylcytosine with 3-Mercaptopropionic Acid and Other Thiols

Authors

  • Martin D. Shetlar,

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    • Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA
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  • Janet Chung

    1. Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA
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    • Current address: City of Hope, Beckman Research Institute, Molecular and Cell Biology, Duarte, CA, USA

Corresponding author email: shetlar@cgl.ucsf.edu (Martin D. Shetlar)

Abstract

The photoproducts from reaction of thymine with cysteine, an amino acid containing a sulfhydryl group, have been studied in detail, whereas results of less extensive studies have been reported for the uracil–cysteine system. However, products arising from corresponding reactions of cytosine and related compounds with compounds containing a sulfhydryl group have not been similarly studied. We report here the results of our study of the photoreaction of 5-methylcytosine (5MeCyt), a minor base occurring in mammalian DNA, with 3-mercaptopropionic acid (3MP), a model compound for cysteine. We found that this reaction proceeds at pH 7 to yield N-(N'-(2′-carboxyethyl)thiocarbamoyl)-3-amino-2-methylacrylamidine (Ia) as a primary photoproduct. A secondary thermal product, identified as 3-(2′-carboxyethylthio)-2-methylacrylamidine (IIa), appears if photoreacted solution is allowed to stand for appreciable times prior to workup; this latter compound is formed via an intermediate product. Heating of purified Ia at 100°C or standing at lower temperatures produces 3-amino-2-methylacrylamidine (IId); similarly, irradiation of Ia with UVB light in aqueous solution converts it into IId. Results from exploratory studies suggest that 5MeCyt similarly reacts with other thiols (2-mercaptoethanol, 2-mercaptoacetic acid) to form analogs of Ia and IIa. Other preliminary results suggest that 5-methyl-2′-deoxycytidine and 1,5-dimethylcytosine photoreact with 3MP to form compounds similar to Ia.

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