Amino Acids

, Volume 48, Issue 4, pp 1087–1098 | Cite as

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

  • Petr Niederhafner
  • Martin Šafařík
  • Eva Brichtová
  • Jaroslav Šebestík
Original Article

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).

Keywords

Nitrotyrosine Peptide synthesis Alpha-synuclein Reaction rate 

Notes

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.

Compliance with ethical standards

Conflict of interest

Authors declare that they have no conflict of interest.

Human participants and animal statement

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.

Supplementary material

726_2015_2163_MOESM1_ESM.pdf (3.8 mb)
Supplementary material 1 (PDF 3894 kb)
726_2015_2163_MOESM2_ESM.gif (221 kb)
Supplementary material 2 (GIF 221 kb)
726_2015_2163_MOESM3_ESM.gif (89 kb)
Supplementary material 3 (GIF 89 kb)

References

  1. Abe K, Pan LH, Watanabe M, Kato T, Itoyama Y (1995) Induction of nitrotyrosine-like immunoreactivity in the lower motor neuron of amyotrophic lateral sclerosis. Neurosci Lett 199(2):152–154CrossRefPubMedGoogle Scholar
  2. Aceña JL, Sorochinsky AE, Soloshonok V (2014) Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases. Part 3: Michael addition reactions and miscellaneous transformations. Amino Acids 46(9):2047–2073CrossRefPubMedGoogle Scholar
  3. Adamson JG, Blaskovich MA, Groenevelt H, Lajoie GA (1991) Simple and convenient synthesis of tert-butyl ethers of Fmoc-serine, Fmoc-threonine, and Fmoc-tyrosine. J Org Chem 56(10):3447–3449CrossRefGoogle Scholar
  4. Allouche AR (2011) Gabedit—a graphical user interface for computational chemistry softwares. J Comput Chem 32:174–182CrossRefPubMedGoogle Scholar
  5. Barlos K, Gatos D, Koutsogianni S, Schafer W, Stavropoulos G, Wenging Y (1991) Darstellung und einsatz von N–Fmoc–O–Trt–hydroxyaminosäuren zur “solid phase” synthese von peptiden. Tetrahedron Lett 32(4):471–474CrossRefGoogle Scholar
  6. Barone V, Cossi M (1998) Quantum calculation of molecular energies and energy gradients in solution by a conductor solvent model. J Phys Chem A 102(11):1995–2001CrossRefGoogle Scholar
  7. Bartesaghi S, Wenzel J, Trujillo M, López M, Joseph J, Kalyanaraman B, Radi R (2010) Lipid peroxyl radicals mediate tyrosine dimerization and nitration in membranes. Chem Res Toxicol 23(4):821–835CrossRefPubMedPubMedCentralGoogle Scholar
  8. Beal MF, Ferrante RJ, Browne SE, Matthews RT, Kowall NW, Brown RH Jr (1997) Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis. Ann Neurol 42(4):644–654CrossRefPubMedGoogle Scholar
  9. Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 98(7):5648–5652CrossRefGoogle Scholar
  10. Beyerman HC, Bontekoe JS (1962) The t-butoxy group, a novel hydroxyl-protecting group for use in peptide synthesis with hydroxy-amino acids. Recl Trav Chim Pays-Bas 81:691–698CrossRefGoogle Scholar
  11. Bodanszky M, Bodanszky A (1994) The practice of peptide synthesis. Springer, Berlin, p 48CrossRefGoogle Scholar
  12. Butterfield DA, Reed T, Sultana R (2011) Roles of 3-nitrotyrosine- and 4-hydroxynonenal-modified brain proteins in the progression and pathogenesis of Alzheimer’s disease. Free Radic Res 45(1):59–72CrossRefPubMedGoogle Scholar
  13. Carpino LA, Han GY (1972) The 9-fluorenylmethoxycarbonyl amino-protecting group. J Org Chem 37(22):3404–3409CrossRefGoogle Scholar
  14. Cossi M, Rega N, Scalmani G, Barone V (2003) Energies, structures, and electronic properties of molecules in solution with the C-PCM solvation model. J Comp Chem 24(6):669–681CrossRefGoogle Scholar
  15. Dear DV, Kazlauskaite J, Meersman F, Oxley D, Webster J, Pinheiro TJT, Gill AC, Bronstein I, Lowe CR (2007) Effects of post-translational modifications on prion protein aggregation and the propagation of scrapie-like characteristics in vitro. Biochim Biophys Acta 1774(7):792–802CrossRefPubMedGoogle Scholar
  16. Erickson BW, Merrifield RB (1973) Use of chlorinated benzyloxycarbonyl protecting groups to eliminate Nε-branching at lysine during solid-phase peptide synthesis. J Am Chem Soc 95(11):3750–3756CrossRefPubMedGoogle Scholar
  17. Exner O, Böhm S (2005) Protonated nitro group: structure, energy and conjugation. Org Biomol Chem 3:1838–1843CrossRefPubMedGoogle Scholar
  18. Fernández AP, Serrano J, Rodrigo J, Monleón E, Monzón M, Vargas A, Badiola JJ, Martínez-Murillo R, Martínez A (2007) Changes in the expression pattern of the nitrergic system of ovine cerebellum affected by scrapie. J Neuropathol Exp Neurol 66(3):196–207CrossRefPubMedGoogle Scholar
  19. Fields GB, Noble RL (1990) Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids. Int J Pept Prot Res 35(3):161–214CrossRefGoogle Scholar
  20. Fletcher S, Gunning PT (2008) Mild, efficient and rapid O-debenzylation of ortho-substituted phenols with trifluoroacetic acid. Tetrahedron Lett 49(33):4817–4819CrossRefGoogle Scholar
  21. Frisch MJ et al (2009) Gaussian 09 revision A1. Gaussian Inc, Wallingford, CTGoogle Scholar
  22. Giasson BI, Duda JE, Murray IVJ, Chen Q, Souza JM, Hurtig HI, Ischiropoulos H, Trojanowski JQ, Lee VM-Y (2000) Oxidative damage linked to neurodegeneration by selective α-synuclein nitration in synucleinopathy lesions. Science 290(5493):985–989CrossRefPubMedGoogle Scholar
  23. Goeshen C, Wibowo N, White JM, Wille U (2011) Damage of aromatic amino acids by the atmospheric free radical oxidant NO3 in the presence of NO2, N2O4, O3 and O2. Org Biomol Chem 9:3380–3385CrossRefGoogle Scholar
  24. Guentchev M, Voigtländer T, Haberler C, Groschup MH, Budka H (2000) Evidence for oxidative stress in experimental prion disease. Neurobiol Dis 7(4):270–273CrossRefPubMedGoogle Scholar
  25. Gurry T, Ullman O, Fisher CK, Perovic I, Pochapsky T, Stultz CM (2013) The dynamic structure of α-synuclein multimers. J Am Chem Soc 135(10):3865–3872CrossRefPubMedGoogle Scholar
  26. Hanson RW, Law HD (1965) O-Benzyl-3-nitrotyrosine and its use in the synthesis of peptides containing 3-nitrotyrosine. J Chem Soc Perkin 1:7297–7304CrossRefGoogle Scholar
  27. Klamt A, Schürmann G (1993) COSMO: a new approach to dielectric screening in solvents with explicit expressions for the screening energy and its gradient. J Chem Soc Perkin Trans 2(5):799–805CrossRefGoogle Scholar
  28. Laurén J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM (2009) Cellular prion protein mediates impairment of synaptic plasticity by amyloid-Β oligomers. Nature 457(7233):1128–1132CrossRefPubMedPubMedCentralGoogle Scholar
  29. Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37(2):785–789CrossRefGoogle Scholar
  30. Lundt BF, Johansen NL, Vølund A, Markussen J (1978) Removal of t-butyl and t-butoxycarbonyl protecting groups with trifluoroacetic acid. Mechanisms, biproduct formation and evaluation of scavengers. Int J Pept Protein Res 12(5):258–268CrossRefPubMedGoogle Scholar
  31. Lüth H-J, Munch G, Arendt T (2002) Aberrant expression of NOS isoforms in Alzheimer’s disease is structurally related to nitrotyrosine formation. Brain Res 953(1–2):135–143CrossRefPubMedGoogle Scholar
  32. Marsh JP, Goodman L (1965) Removal of O-benzyl blocking groups with trifluoroacetic acid. J Org Chem 30(7):2491–2492CrossRefGoogle Scholar
  33. Martins VR, Beraldo FH, Hajj GN, Lopes MH, Lee KS, Prado MA, Linden R (2010) Prion protein: orchestrating neurotrophic activities. Curr Issues Mol Biol 12(2):63–86PubMedGoogle Scholar
  34. Mathias LJ (1979) Esterification and alkylation reactions employing isoureas. Synthesis 8:561–576CrossRefGoogle Scholar
  35. Miehlich B, Savin A, Stoll H, Preuss H (1989) Results obtained with the correlation energy density functionals of Becke and Lee, Yang and Parr. Chem Phys Lett 157(3):200–206CrossRefGoogle Scholar
  36. Mittoo S, Sundstrom LE, Bradley M (2003) Synthesis and evaluation of fluorescent probes for the detection of calpain activity. Anal Biochem 319(2):234–238CrossRefPubMedGoogle Scholar
  37. Pennathur S, Jackson-Lewis C, Przedborski S, Heinecke JW (1999) Mass spectrometric quantification of 3-nitrotyrosine, ortho-tyrosine, and o, o’-dityrosine in brain tissue of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, a model of oxidative stress in Parkinson’s disease. J Biol Chem 274(49):34621–34628CrossRefPubMedGoogle Scholar
  38. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem 25(13):1605–1612CrossRefPubMedGoogle Scholar
  39. Pícha J, Vaněk V, Buděšínský M, Mládková J, Garrow TA, Jiráček J (2013) The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase. Eur J Med Chem 65:256–275CrossRefPubMedGoogle Scholar
  40. Prusiner SB (1998) Prions. Proc Natl Acad Sci USA 95(23):13363–13383CrossRefPubMedPubMedCentralGoogle Scholar
  41. Radi R (2004) Nitric oxide, oxidants, and protein tyrosine nitration. Proc Natl Acad Sci USA 101(12):4003–4008CrossRefPubMedPubMedCentralGoogle Scholar
  42. Radi R (2013) Protein tyrosine nitration: biochemical mechanisms and structural basis of functional effects. Acc Chem Res 46(2):550–559CrossRefPubMedPubMedCentralGoogle Scholar
  43. Robinson RAS, Evans AR (2012) Enhanced sample multiplexing for nitrotyrosine-modified proteins using combined precursor isotopic labeling and isobaric tagging. Anal Chem 84(11):4677–4686CrossRefPubMedGoogle Scholar
  44. Sacksteder CA, Qian W-J, Knyushko TV, Wang H, Chin MH, Lacan G, Melega WP, Camp DG II, Smith DJ, Squier TC, Bigelow DJ (2006) Endogenously nitrated proteins in mouse brain: links to neurodegenerative disease. Biochem 45(26):8009–8022CrossRefGoogle Scholar
  45. Sever MJ, Wilker JJ (2001) Synthesis of peptides containing DOPA (3,4-dihydroxyphenylalanine). Tetrahedron 57(29):6139–6146CrossRefGoogle Scholar
  46. Soloshonok VA, Cai C, Hruby VJ, Van Meervelt L, Mischenko N (1999) Stereochemically defined C-substituted glutamic acids and their derivatives. 1. An efficient asymmetric synthesis of (2S,3S)-3-methyl- and -3-trifluoromethylpyroglutamic acids. Tetrahedron 55(41):12031–12044CrossRefGoogle Scholar
  47. Song Y-L, Peach ML, Roller PP, Qiu S, Wang S, Long Y-Q (2006) Discovery of a novel nonphosphorylated pentapeptide motif displaying high affinity for Grb2-SH2 domain by the utilization of 3′-substituted tyrosine derivatives. J Med Chem 49(5):1585–1596CrossRefPubMedGoogle Scholar
  48. Sorochinsky AE, Aceña JL, Moriwaki H, Sato T, Soloshonok VA (2013a) Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases; part 1: alkyl halide alkylations. Amino Acids 45(4):691–718CrossRefPubMedGoogle Scholar
  49. Sorochinsky AE, Aceña JL, Moriwaki H, Sato T, Soloshonok V (2013b) Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases. Part 2: Aldol, Mannich addition reactions, deracemization and (S) to (R) interconversion of α-amino acids. Amino Acids 45(5):1017–1033CrossRefPubMedGoogle Scholar
  50. Strong MJ, Sopper MM, Crow JP, Strong WL, Beckman JS (1998) Nitration of the low molecular weight neurofilament is equivalent in sporadic amyotropic lateral sclerosis and control cervical spinal cord. Biochem Biophys Res Commun 248(1):157–164CrossRefPubMedGoogle Scholar
  51. Tam JP, Heath WF, Merrifield RB (1983) SN 1 and SN 2 mechanisms for the deprotection of synthetic peptides by hydrogen fluoride. Studies to minimize the tyrosine alkylation side reaction. Int J Pept Protein Res 21(1):57–65CrossRefPubMedGoogle Scholar
  52. Tomasi J, Mennucci B, Cammi R (2005) Quantum mechanical continuum solvation models. Chem Rev 105(8):2999–3093CrossRefPubMedGoogle Scholar
  53. Vosko SH, Wilk L, Nusair M (1980) Accurate spin-dependent electron liquid correlation energies for local spin density calculations: a critical analysis. Can J Phys 58(8):1200–1211CrossRefGoogle Scholar
  54. Yamashiro D, Li CH (1973) Adrenocorticotropins. 44. Total synthesis of the human hormone by the solid-phase method. J Am Chem Soc 95(4):1310–1315CrossRefPubMedGoogle Scholar
  55. Zawada Z, Šebestík J, Šafařík M, Bouř P (2011) Dependence of the reactivity of acridine on its substituents: a computational and kinetic study. Eur J Org Chem 34:6989–6997CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Petr Niederhafner
    • 1
    • 2
  • Martin Šafařík
    • 2
  • Eva Brichtová
    • 2
  • Jaroslav Šebestík
    • 2
  1. 1.Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical TechnologyUniversity of Chemistry and Technology, PraguePrague 6Czech Republic
  2. 2.Institute of Organic Chemistry and BiochemistryAcademy of SciencesPrague 6Czech Republic

Personalised recommendations