A NOVEL-APPROACH FOR THE SYNTHESIS OF TYR OSINE SULFATE-CONTAINING PEPTIDES USING A SAFETY CATCH TYPE PROTECTING GROUP AS A KEY FEATURE

Dimethylformamide-sulfur trioxide (DMF-SO3) complex was found to be mo re suitable for tyrosine sulfation than pyridine-sulfur trioxide (pyri dine-SO3) complex, the most commonly used sulfur trioxide complex for sulfation. In addition, a new method for the effective reduction of me thionine sulfoxide [Met(O)] in protected peptides was established usin g DMF-SO3 complex in the presence of nucleophile such as thiol or iodi de ion. Based on these findings concerning DMF-SO3 complex, a unique s ynthetic method for tyrosine-sulfate [Tyr(SO3H)] containing peptide wa s developed. In this methodology, the P-(methylsulfinyl) benzyl : (Msi b) group, a safety-catch type protecting group, was used as a key prot ecting group for the alcoholic hydroxyl function of Ser/Thr in order t o achieve the selective sulfation on Tyr. An effective acidic deprotec tion system to minimize the decomposition of sulfate ester on Tyr(SO3H ) residue was also developed. Several biologically active Tyr(SO3H)-co ntaining peptides were prepared by this new method.