高付加価値ペプチド合成のための最終脱保護法の開発と細胞内情報伝達機構解明への展開研究
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概要
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This review summarizes the development of deprotecting methodologies for peptides and their practical application to the synthesis of disulfide bond- or phosphoamino acid-containing peptides. Acidic deprotecting systems utilizing Brφnsted acid (HF, trifluoromethanesulfonic acid (TFMSA) and HBr etc.) have been used for the removal of protecting groups in peptide chemistry; however, these reagents are not always applicable to all of the peptides including cystine- or phosphoamino acid-containing peptides. Our attempt to utilize Lewis acid for the deprotective reaction resulted in the development of efficient and practical reagent systems (1 M trimethylsilyl trifluoromethanesulfonate (TMSOTf)-sulfide in trifluoroacetic acid (TFA) and 1 M trimethylsilyl bromide (TMSBr)-sulfide in TFA) suitable for peptide synthesis. A new disulfide bond-forming reaction using Tl(OCOCF_3)_3 was developed for the synthesis of cystine peptides. The use of TMSOTf or TMSBr-mediated deprotecting system in conjunction with the disulfide bond-forming reaction utilizing Tl(III) provides a procedure for the practical synthesis of cystine peptides. A two-step deprotection method consisting of high acidic (1 M TMSOTf-thioanisole in TFA, m-cresol, ethanedithiol) and low acidic (high acidic system + dimethyl sulfide - TMSOTf) treatments was successfully applied to the deprotection of protected phosphopeptide with dimethylprotected phosphoamino acids. Furthermore, we synthesized phosphatase-resistant phosphoamino acid isosters bearing the substitution of a phosphate oxygen with a difluoromethylene. The syntheses of peptides possessing these nonhydrolyzable phosphoamino acids were achieved utilizing two-step deprotecting methodologies. Additionally, we demonstrated the usefulness of phosphatase-resistant phosphopeptides as biochemical tools for understanding signal transduction.
- 公益社団法人日本薬学会の論文
- 2000-01-01
著者
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Omagari Akane
Graduate School Of Pharmaceutical Sciences Kyoto University
-
Otaka Akira
Univ. Tokushima Tokushima Jpn
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大高 章
京都大学大学院薬学研究科
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- 高付加価値ペプチド合成のための最終脱保護法の開発と細胞内情報伝達機構解明への展開研究