Large-scale, protection-free synthesis of Se-adenosyl-L-selenomethionine analogues and their application as cofactor surrogates of methyltransferases.
S-adenosyl-L-methionine (SAM) analogues have previously demonstrated their utility as chemical reporters of methyltransferases. Here we describe the facile, large-scale synthesis of Se-alkyl Se-adenosyl-L-selenomethionine (SeAM) analogues and their precursor, Se-adenosyl-L-selenohomocysteine (SeAH). Comparison of SeAM analogues with their equivalent SAM analogues suggests that sulfonium-to-selenonium substitution can enhance their compatibility with certain protein methyltransferases, favoring otherwise less reactive SAM analogues. Ready access to SeAH therefore enables further application of SeAM analogues as chemical reporters of diverse methyltransferases.
Molecular Pharmacology and Chemistry Program and ‡Tri-Institutional Training Program in Chemical Biology, Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.
Ian R
IR
Bothwell
Minkui
M
Luo
D008780:Methyltransferases / Q000737:chemistry*; D015394:Molecular Structure; D017279:Selenocysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D012645:Selenomethionine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
D017279:Selenocysteine; D012645:Selenomethionine; D008780:Methyltransferases; C002979:selenomethylselenocysteine