1997 Fiscal Year Final Research Report Summary
Development of Practical Synthetic Method for Phosphopeptides using Two-step Deprotecting Procedures
| Project/Area Number |
08672421
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
OTAKA Akira Kyoto University Graduate School of Pharmaceutical Sciences Associate Professor, 薬学研究科, 助教授 (20201973)
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| Co-Investigator(Kenkyū-buntansha) |
TAMAMURA Hirokazu Kyoto University, Graduate School of Pharmaceutical Sciences Assistant Professor, 薬学研究科, 講師 (80217182)
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| Project Period (FY) |
1996 – 1997
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| Keywords | phosphoamino acid / phosphopeptides / peptide synthesis / final deprotection / dimethylphosphono amino acids |
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| Research Abstract |
A protocol has been developed for the synthesis of peptides containing O-phosphorylated tyrosines, serines, and/or threonines. The procedure involves incorporation of dimethyl-protected phosphorylated amino acid derivatives into peptides using Boc chemistry and subsequent removal of Me groups using a two-step deprotection method consisting of high acidic and low acidic treatments. Optimized deprotection conditions for the protected resins were established, which consist of a combination of the first-step reagent (1 M TMSOTf-thioanisole in TFA,m-cresol, EDT) and the second-step reagent (first-step reagent + DMS-TMSOTf). Furthermore, the second-step reagent can be changed to the more effective reagent system (TMSOTf-DMS-m-cresol-EDT). Theses synthetic method afforded phosphoamino acid-containing peptide in high yield without significant accompanying side reactions. For a phosphoprotein synthesis, we developed SN1-deprotecting procedure (TFMSA-TFA-m-cresol). Treatment of protcted phosphopeptide thioester resins with this system afforded protected phosphopeptide thioesters, in which side chains of Lys and phosphoamino were protected with CLZ or Me grpoups, respectively. Synthetic studies on phosphoprotein utilizing protected phosphopeptide thioesters are in progress.
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