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Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

Vladimir Kubyshkin and Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457. https://doi.org/10.3762/bjoc.13.241

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Supporting Information File 1: Amide equilibrium constants (Table S1) and copies of the NMR and CD spectra.
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Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

Vladimir Kubyshkin and Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457. https://doi.org/10.3762/bjoc.13.241

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Kubyshkin, V.; Budisa, N. Beilstein J. Org. Chem. 2017, 13, 2442–2457. doi:10.3762/bjoc.13.241

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TY  - JOUR
A1  - Kubyshkin, Vladimir
A1  - Budisa, Nediljko
T1  - Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models
JF  - Beilstein Journal of Organic Chemistry
PY  - 2017///
VL  - 13
SP  - 2442
EP  - 2457
SN  - 1860-5397
DO  - 10.3762/bjoc.13.241
PB  - Beilstein-Institut
JA  - Beilstein J. Org. Chem.
UR  - https://doi.org/10.3762/bjoc.13.241
KW  - conformation
KW  - ester bond
KW  - hydrolysis
KW  - peptides
KW  - polarity
N2  - Fluorinated moieties are highly valuable to chemists due to the sensitive NMR detectability of the 19F nucleus. Fluorination of molecular scaffolds can also selectively influence a molecule’s polarity, conformational preferences and chemical reactivity, properties that can be exploited for various chemical applications. A powerful route for incorporating fluorine atoms in biomolecules is last-stage fluorination of peptide scaffolds. One of these methods involves esterification of the C-terminus of peptides using a diazomethane species. Here, we provide an investigation of the physicochemical consequences of peptide esterification with partially fluorinated ethyl groups. Derivatives of N-acetylproline are used to model the effects of fluorination on the lipophilicity, hydrolytic stability and on conformational properties. The conformational impact of the 2,2-difluoromethyl ester on several neutral and charged oligopeptides was also investigated. Our results demonstrate that partially fluorinated esters undergo variable hydrolysis in biologically relevant buffers. The hydrolytic stability can be tailored over a broad pH range by varying the number of fluorine atoms in the ester moiety or by introducing adjacent charges in the peptide sequence.
ER  -

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