The absolute configuration at the sulfonium center of naturally occurring S-adenosylmethionine has been determined. The diastereomeric mixture of S-carboxymethylmethionine salts from reaction of (S)-methionine with iodoacetic acid was resolved by crystallization of the polyiodides (probably pentaiodides) into (R)-and (S)-[((3S)-3-amino-3-carboxypropyl)-(carboxymethyl)methylsulfonium] salts, and these were converted into the 2,4,6-trinitrobenzenesulfonates. All four salts were characterized. The crystal structure of (R)-[((3S)-3-amino-3-carboxypropyl)(carboxymethyl)methylsulfonium] 2,4,6-trinitrobenzenesulfonate was studied by x-ray diffraction and the relative and absolute configurations at the two asymmetric centers were established. The crystals are triclinic belonging to the space group P1 and each unit cell contains two molecular ion pairs in closely similar conformations. The unit cell dimensions are a=5.408 (2), b=11.061 (3), c=18.317 (3) Å; α=105.06° (2), β=91.50° (2), γ=106.50° (2). The structure, including the absolute configuration, was determined and refined to R=0.070. [14CH3]-S-Adenosylmethionine, prepared enzymatically, was cleaved successively by dilute alkali and by sodium periodate. On chromatography of the product, a strong peak of radioactivity was eluted at the retention time of (S)-[((3S)-3-amino-3-carboxypropyl)(carboxymethyl)methylsulfonium] ion, with minimal radioactivity at the retention time of the (R)-sulfonium diastereomer. The radioactivity cocrystallized with the 2,4,6-trinitrobenzenesulfonate of the (S)-sulfonium diastereomer and was lost almost completely on crystallization with the (R)-sulfonium diastereomer. It was deduced that natural S-adenosylmethionine is 5'-[((3S)-3-amino-3-carboxypropyl)methyl-(S)-sulfonio]-5'-deoxyadenosine; that is, it had the S configuration at sulfur.
ASJC Scopus subject areas
- Colloid and Surface Chemistry