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Issue 13, 2016
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A perfluoroaromatic abiotic analog of H2 relaxin enabled by rapid flow-based peptide synthesis

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Abstract

H2 relaxin is a pleiotropic peptide hormone with clinical potential. Here we report on the reaction and use of hexafluorobenzene as an intramolecular disulfide replacement between Cys10 and Cys15 in the A-chain of H2 relaxin. Using flow-based Fmoc solid-phase peptide synthesis methodology we were able to obtain high-quality H2 relaxin fragments that were previously reported as challenging to synthesize. Subsequent native chemical ligation and oxidative folding enabled total synthesis of both wild type H2 relaxin and a C6F4 linked analog. Cell-based activity assays revealed modest activity for the C6F4 linked H2 relaxin analog, albeit 100-fold reduced relative to wild type. This work demonstrates how perfluoroarylation-cysteine SNAr chemistry may be a useful tool for the selective replacement of native disulfide bonds in proteins.

Graphical abstract: A perfluoroaromatic abiotic analog of H2 relaxin enabled by rapid flow-based peptide synthesis

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Publication details

The article was received on 26 Jan 2016, accepted on 01 Mar 2016 and first published on 04 Mar 2016


Article type: Communication
DOI: 10.1039/C6OB00208K
Citation: Org. Biomol. Chem., 2016,14, 3345-3349

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    A perfluoroaromatic abiotic analog of H2 relaxin enabled by rapid flow-based peptide synthesis

    T. Lühmann, S. K. Mong, M. D. Simon, L. Meinel and B. L. Pentelute, Org. Biomol. Chem., 2016, 14, 3345
    DOI: 10.1039/C6OB00208K

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