Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/81888
Title: Biomimetic synthesis of cyclic peptides using novel thioester surrogates
Authors: Hemu, Xinya
Taichi, Misako
Qiu, Yibo
Liu, Ding-Xiang
Tam, James P.
Keywords: Thioester
N-S acyl shift
Intein mimetic
Cyclic peptides
Conotoxin
Sunflower trypsin inhibitor
Thioethylamido
Thioester surrogate
Issue Date: 2013
Source: Hemu, X., Taichi, M., Qiu, Y., Liu, D.-X., & Tam, J. P. (2013). Biomimetic synthesis of cyclic peptides using novel thioester surrogates. Biopolymers, 100(5), 492-501.
Series/Report no.: Biopolymers
Abstract: Acyl shifts involving N-S and S-S rearrangements are reactions central to the breaking of a peptide bond and forming of thioester intermediates in an intein-catalyzed protein splicing that ultimately leads to the formation of a new peptide bond by an uncatalyzed S-N acyl shift reaction. To mimic these three acyl shift reactions in forming thioesters and the subsequent peptide ligation, here we describe the development of two 9-fluorenylmethoxycarbonyl (Fmoc)-compatible thioester surrogates that can undergo uncatalyzed N-S, S-S, and S-N acyl shifts for preparing thioesters and cyclic peptides. These surrogates were incorporated as a C-terminal amido moiety of a target peptide using Fmoc chemistry by solid-phase synthesis, and then transformed into a thioester or thiolactones via two acyl shift reactions with or without the presence of an external thiol under acidic conditions. The proposed intein-mimetic thioester surrogates were prepared using readily available starting materials including N-methyl cysteine or 2-thioethylbutylamide. A key functional moiety shared in their design is the thioethylamido (TEA) moiety, which is essential to effect a proximity-driven N-S acyl shift under a favorable five-member ring transition in the breaking of a peptide bond. Thus, the tandem series of acyl shifts effected by a TEA moiety in a thioester surrogate together with a thioethylamino moiety of an N-terminal Cys residue in a linear peptide precursor are chemical mimics of an intein, as they mediate both excision and ligation reactions in forming cyclic peptides including cyclic conotoxin and sunflower trypsin inhibitor described herein.
URI: https://hdl.handle.net/10356/81888
http://hdl.handle.net/10220/39685
ISSN: 0006-3525
DOI: 10.1002/bip.22308
Rights: © 2013 Wiley Periodicals, Inc. This is the author created version of a work that has been peer reviewed and accepted for publication by Biopolymers, Wiley Periodicals, Inc. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1002/bip.22308].
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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