Ring-opening photoreactions of 5-methylcytosine with 3-mercaptopropionic acid and other thiols

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.