title: Rapid acidolysis of benzyl group as a suitable approach for syntheses of peptides naturally produced by oxidative stress and containing 3-nitrotyrosine.
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).
authors.affiliation: 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.|Institute of Organic Chemistry and Biochemistry, Academy of Sciences, Flemingovo náměstí 2, 16610, Prague 6, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Niederhafner
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences, Flemingovo náměstí 2, 16610, Prague 6, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Šafařík
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences, Flemingovo náměstí 2, 16610, Prague 6, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Brichtová
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences, Flemingovo náměstí 2, 16610, Prague 6, Czech Republic. jsebestik@seznam.cz.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Šebestík
mesh_terms: D000595:Amino Acid Sequence; D005449:Fluorenes / Q000737:chemistry; D006868:Hydrolysis; D018384:Oxidative Stress; D010455:Peptides / Q000737:chemistry*; D011328:Prions / Q000737:chemistry*; D014269:Trifluoroacetic Acid / Q000737:chemistry; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D005449:Fluorenes; D010455:Peptides; D011328:Prions; D051844:alpha-Synuclein; C002744:3-nitrotyrosine; D014443:Tyrosine; D014269:Trifluoroacetic Acid
keywords: Alpha-synuclein; Nitrotyrosine; Peptide synthesis; Reaction rate