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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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).
KeywordsNitrotyrosine Peptide synthesis Alpha-synuclein Reaction rate
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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Authors declare that they have no conflict of interest.
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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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