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Synlett 2017; 28(14): 1780-1784
DOI: 10.1055/s-0036-1589037
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© Georg Thieme Verlag Stuttgart · New York

Improved Fmoc Solid-Phase Peptide Synthesis of Oxytocin with High Bioactivity

Pengcheng Sun
College of Oceanography, Hainan University, Haikou, Hainan Province, 570228, P. R. of China   Email: bhhu@hainu.edu.cn
,
Wenli Tang
College of Oceanography, Hainan University, Haikou, Hainan Province, 570228, P. R. of China   Email: bhhu@hainu.edu.cn
,
Yu Huang
College of Oceanography, Hainan University, Haikou, Hainan Province, 570228, P. R. of China   Email: bhhu@hainu.edu.cn
,
Bi-Huang Hu*
College of Oceanography, Hainan University, Haikou, Hainan Province, 570228, P. R. of China   Email: bhhu@hainu.edu.cn
› Author AffiliationsThis work was supported by the Hainan Provincial Program for High-level Innovative Talents Grant HN2011
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Publication History

Received: 08 April 2017

Accepted after revision: 04 May 2017

Publication Date:
31 May 2017 (online)

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Abstract

We described here the synthesis of oxytocin by an improved Fmoc solid-phase peptide synthesis (SPPS) method with a Rink-Amide resin as the solid support, HBTU as the coupling reagent, Fmoc-protected amino acids as the building blocks, and piperazine for Fmoc removal as a substitute for the standard reagent piperidine. Unlike previously reported syntheses, the removal of the S-Acm protecting group of Cys and cyclization forming the disulfide bond were carried out by using iodine on the resin with the fully protected peptide chains. Finally, a crude oxytocin with a purity of 92% was obtained by simultaneous cleavage of the peptide chains from the resin and removal of all side-chain protecting groups with trifluoroacetic acid containing the scavengers (yield 85%). The crude peptide was purified by using preparative RP-HPLC to obtain oxytocin (high purity 99.3%) with a bioactivity of 588 IU/mg, the highest reported so far in the literature. This investigation provides a contribution in efforts for the large-scale synthesis of oxytocin in high purity under mild conditions with iodine for on-resin disulfide bond formation and a substitute for the standard Fmoc-deprotecting reagent piperidine, a controlled substance.

Key words

oxytocin - Fmoc solid-phase peptide synthesis - on-resin cyclization - disulfide bond formation by iodine - piperazine

Supporting Information

    Supporting information for this article is available online at https://doi.org /10.1055/s-0036-1589037.
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