Synthetic Procedure for N-Fmoc Amino Acyl-N-Sulfanylethylaniline Linker as Crypto-Peptide Thioester Precursor with Application to Native Chemical Ligation

详细信息    查看全文

• 作者：Ken Sakamoto ; Kohei Sato ; Akira Shigenaga ; Kohei Tsuji ; Shugo Tsuda ; Hajime Hibino ; Yuji Nishiuchi ; Akira Otaka
• 刊名：The Journal of Organic Chemistry
• 出版年：2012
• 出版时间：August 17, 2012
• 年：2012
• 卷：77
• 期：16
• 页码：6948-6958
• 全文大小：420K
• 年卷期：v.77,no.16(August 17, 2012)
• ISSN：1520-6904

文摘

N-Sulfanylethylanilide (SEAlide) peptides 1, obtainable using Fmoc-based solid-phase peptide synthesis (Fmoc SPPS), function as crypto-thioesters in native chemical ligation (NCL), yielding a wide variety of peptides/proteins. Their acylating potential with N-terminal cysteinyl peptides 2 can be tuned by the presence or absence of phosphate salts, leading to one-pot/multifragment ligation, operating under kinetically controlled conditions. SEAlide peptides have already been shown to be promising for use in protein synthesis; however, a widely applicable method for the synthesis of N-Fmoc amino acyl-N-sulfanylethylaniline linkers 4, required for the preparation of SEAlide peptides, is unavailable. The present study addresses the development of efficient condensation protocols of 20 naturally occurring amino acid derivatives to the N-sulfanylethylaniline linker 5. N-Fmoc amino acyl aniline linkers 4 of practical use in NCL chemistry, except in the case of the proline- or aspartic acid-containing linker, were successfully synthesized by coupling of POCl₃- or SOCl₂-activated Fmoc amino acid derivatives with sodium anilide species 6, without accompanying racemization and loss of side-chain protection. Furthermore, SEAlide peptides 7 possessing various C-terminal amino acids (Gly, His, Phe, Ala, Asn, Ser, Glu, and Val) were shown to be of practical use in NCL chemistry.