A novel N-terminal degradation reaction of peptides via N-amidination

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• 作者：Yoshio Hamada ; ^{pynden@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Amide bond cleavage ; Edman degradation ; N-amidination ; N-Amidinopeptide ; N-terminal degradation
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 April 2016
• 年：2016
• 卷：26
• 期：7
• 页码：1690-1695
• 全文大小：1705 K

文摘

The cleavage of amide bonds requires considerable energy. It is difficult to cleave the amide bonds in peptides at room temperature, whereas ester bonds are cleaved easily. If peptide bonds can be selectively cleaved at room temperature, it will become a powerful tool for life science research, peptide prodrug, and tissue-targeting drug delivery systems. To cleave a specific amide bond at room temperature, the decomposition reaction of arginine methyl ester was investigated. Arginine methyl ester forms a dimer; the dimer releases a heterocyclic compound and ornithine methyl ester at room temperature. We designed and synthesized N-amidinopeptides based on the decomposition reaction of arginine methyl ester. Alanyl-alanine anilide was used as the model peptide and could be converted into N-degraded peptide, alanine anilide, via an N-amidination reaction at close to room temperature. Although the cleavage rate in pH 7.4 phosphate buffered saline (PBS) at 37 °C was slow (t_1/2 = 35.7 h), a rapid cleavage rate was observed in 2% NaOH aq (t_1/2 = 1.5 min). To evaluate the versatility of this reaction, a series of peptides with Lys, Glu, Ser, Cys, Tyr, Val, and Pro residue at the N-terminal were synthesized; they showed rapid cleavage rates of t_1/2 values from 1 min to 10 min.