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Rapid acidolysis of benzyl group as a suitable approach for syntheses of peptides naturally produced by oxidative stress and containing 3-nitrotyrosine

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A Correction to this article was published on 25 October 2019

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Abstract

3-Nitrotyrosine (Nit) belongs to products of oxidative stress and could probably influence conformation of neurodegenerative proteins. Syntheses of peptides require availability of suitable synthon for introduction of Nit residue. Common phenolic protection groups are more acid labile, when they are attached to Nit residue. We have found that Fmoc–Nit(Bn)–OH is a good building block for syntheses of Nit containing peptides by Fmoc/tBu strategy. Interestingly, the peptides containing multiple Nit residues can be available solely by use of Fmoc–Nit(Bn)–OH synthon. Bn is removed rapidly with ca 80 % trifluoroacetic acid in dark. The cleavage of Bn from Fmoc–Nit(Bn)–OH proceeds via pseudo-first order mechanism with activation barrier 32 kcal mol−1 and rate k = 15.3 s−1 at 20 °C. This rate is more than 2,000,000 times faster than that for cleavage of benzyl from Tyr(Bn).

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Change history

  • 25 October 2019

    This errata is for paper ���Rapid acidolysis of benzyl group as a suitable approach for syntheses

  • 25 October 2019

    This errata is for paper ���Rapid acidolysis of benzyl group as a suitable approach for syntheses

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Acknowledgments

This work was supported by the Czech Science Foundation (14-00431S), Research Project RVO 61388963, and MetaCentrum computational resources (LM2010005 and CZ.1.05/3.2.00/08.0144). E.B. and J.Š. were also supported by project Open Science IV (CZ.1.07/2.3.00/35.0023). Molecular visualization was carried out with the UCSF Chimera package (Pettersen et al. 2004). Chimera is developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIGMS P41-GM103311). TS search was visualized using program MOLDEN. Vibrations were visualized using program Gabedit (Allouche 2011). We thank Dr. Jan Ježek, Ph. D. for corrections of English language, Mrs. Miroslava Blechová, M. Sc. for automatized peptide synthesis, and Mr. Pavel Fiedler, M. Sc. for IR spectra measurement.

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  1. Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology, University of Chemistry and Technology, Prague, Technická 5, 166 28, Prague 6, Czech Republic

    Petr Niederhafner

  2. Institute of Organic Chemistry and Biochemistry, Academy of Sciences, Flemingovo náměstí 2, 16610, Prague 6, Czech Republic

    Petr Niederhafner, Martin Šafařík, Eva Brichtová & Jaroslav Šebestík

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  1. Petr Niederhafner
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Correspondence to Jaroslav Šebestík.

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This paper does not contain any studies with human participants or animals performed by any of the authors. For this type of study formal consent is not required.

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Handling Editor: V. Soloshonok.

Standard abbreviations have been followed throughout this paper (J Peptide Sci 12:1–12, 2006). Unless stated otherwise, amino acids are of L-configuration.

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Supporting figures, movies and reproductions of 1H and 13C NMR, IR and UV-Vis spectra of stable compounds. XYZ coordinates and energies of calculated compounds and ions. Movie 001 shows identification of transition state by step-wise prolongation of C–O bond by 0.05 Å. Further refinement of step down to 0.0005 Å did not lead to identification of another transition state (not shown). Movie 002 shows vibration of transition state along the imaginary frequency.

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Niederhafner, P., Šafařík, M., Brichtová, E. et al. Rapid acidolysis of benzyl group as a suitable approach for syntheses of peptides naturally produced by oxidative stress and containing 3-nitrotyrosine. Amino Acids 48, 1087–1098 (2016). https://doi.org/10.1007/s00726-015-2163-2

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