The chemical synthesis of high specific-activity [35S]adenosylhomocysteine

The study of the family of transmethylases, critical to normal cellular function and often altered in cancer, can be facilitated by the availability of a high specific-activity S-adenosylhomocysteine. We report the two-step preparation of 35S]adenosylhomocysteine from 35S]methionine at a specific activity of 1420 Ci/mmol in an overall yield of 24% by a procedure involving demethylation of the 35S]methionine to 35S]homocysteine followed by condensation with 5'-chloro-5'-deoxyadenosine. The ease of the reactions, ready availability and low cost of the reagents and high specific-activity and stability of the product make the procedure an attractive one with many uses, and superior to current methodology.