Journal
ORGANIC & BIOMOLECULAR CHEMISTRY
Volume 14, Issue 13, Pages 3345-3349Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c6ob00208k
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Funding
- MIT startup funds
- Sontag Foundation Distinguished Scientist Award
- MIT/NIGMS Biotechnology Training Program [5T32GM008334-25]
- Bayerische Forschungsstiftung
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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.
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