As a part of the research to create novel therapeutic peptides, there are numerous interests toward their C-terminal functionalization, including amidation and head-to-tail cyclization, which might improve their bioavailability. In addition, practical synthetic methods to enable the large-scale production of peptides are highly required.We have developed hydrophobic tag-assisted liquid-phase peptide synthesis. In this strategy, the reaction proceeds effectively in less polar solvents. Tag-attached peptide can be isolated as precipitate through the addition of polar solvents, which enables easy separation/purification.Here we report the applications of this strategy toward the synthesis of head-to-tail cyclized and C-alkylamidated peptide. Initially, Fmoc-(A.A)n-OH was efficiently introduced to the N-hydrophobically-tagged glycine methyl ester (1) and ethylamine (2). Based on these compounds, peptide elongation via Fmoc strategy was conducted to give corresponding peptide precursors in 86% and 78% yield, respectively. The results of peptide cyclization and N-terminal modification will be discussed in detail.

Hydrophobic tag-assisted liquid-phase peptide synthesis: An application toward <i>C</i>-terminus modification

246th National Meeting (2013)

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Hydrophobic tag-assisted liquid-phase peptide synthesis: An application toward C-terminus modification