Oxidative stress can lead to various derivatives of the tyrosine residue in peptides and proteins. A typical product is 3-nitro-L-tyrosine residue (Nit), which can affect protein behavior during neurodegenerative processes, such as those associated with Alzheimer's and Parkinson's diseases. Surface enhanced Raman spectroscopy (SERS) is a technique with potential for detecting peptides and their metabolic products at very low concentrations. To explore the applicability to Nit, we use SERS to monitor tyrosine nitration in Met-Enkephalin, rev-Prion protein, and α-synuclein models. Useful nitration indicators were the intensity ratio of two tyrosine marker bands at 825 and 870 cm-1 and a bending vibration of the nitro group. During the SERS measurement, a conversion of nitrotyrosine to azobenzene containing peptides was observed. The interpretation of the spectra has been based on density functional theory (DFT) simulations. The CAM-B3LYP and ωB97XD functionals were found to be most suitable for modeling the measured data. The secondary structure of the α-synuclein models was monitored by electronic and vibrational circular dichroism (ECD and VCD) spectroscopies and modeled by molecular dynamics (MD) simulations. The results suggest that the nitration in these peptides has a limited effect on the secondary structure, but may trigger their aggregation.

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

Department of Chemistry University of Illinois at Chicago 845 W Taylor St Chicago IL 60607 7061 USA

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

Zobrazit více v PubMed

Abello N, Kerstjens HA, Postma DS, Bischoff R (2009) Protein tyrosine nitration: Selectivity, physicochemical and biological consequences, dinitration and proteomic methods for the identification of tyrosine-nitrated proteins. J Proteome Res 8(7):3222–3238 PubMed

Alvarez-Puebla RA, Contreras-Caceres R, Pastoriza-Santos I, Perez-Juste J, Liz-Marzan LM (2009) Au@pNIPAM colloids as a molecular traps for surface-enhanced, spectroscopic, ultra-sensitive analysis. Angew Chem Int Ed 48(1):138–143

Anderson JP, Walker DE, Goldstein JM, de Laat R, Banducci K, Caccavello RJ, Barbour R, Huang J, Kling K, Lee M, Diep L, Keim PS, Shen X, Chataway T, Schlossmacher MG, Seubert P, Schenk D, Sinha S, Gai WP, Chilcote TJ (2006) Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J Biol Chem 281:29739–29752 PubMed

Aslan M, Dogan S (2011) Proteomic detection of nitroproteins as potential biomarkers for cardiovascular disease. J Proteomics 74(11):2274–2288 PubMed

Barron LD (2012) From cosmic chirality to protein structure: Lord Kelvin’s legacy. Chirality 24(11):879–893 PubMed

Barron LD, Buckingham AD (2010) Vibrational optical activity. Chem Phys Lett 492(4–6):199–213

Barron LD, Hecht L, Blanch EW, Bell AF (2000) Solution structure and dynamics of biomolecules from Raman optical activity. Prog Biophys Mol Biol 73(1):1–49 PubMed

Barron LD, Hecht L, McColl IH, Blanch EW (2004) Raman optical activity comes of age. Mol Phys 102(8):731–744

Barron LD, Zhu F, Hecht L (2006) Raman optical activity: An incisive probe of chirality, and of biomolecular structure and behaviour. Vib Spectrosc 42(1):15–24

Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 98(7):5648–5652

Beckman JS, Crow JP (1993) Pathological implications of nitric oxide, superoxide and peroxynitrite formation. Biochem Soc Trans 21(2):330–334 PubMed

Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87(4):1620–1624 PubMed

Betz JF, Yu WW, Cheng Y, White IM, Rubloff GW (2014) Simple SERS substrates: powerful, portable, and full of potential. Phys Chem Chem Phys 16(6):2224–2239 PubMed

Bodanszky M, Bodanszky A (1994) The practice of peptide synthesis. Springer, Berlin, p 48

Boese AD, Martin JML (2004) Development of density functionals for thermochemical kinetics. J Chem Phys 121(8):3405–3416 PubMed

Bouř P, Keiderling TA (2002) Partial optimization of molecular geometry in normal coordinates and use as a tool for simulation of vibrational spectra. J Chem Phys 117(9):4126–4132

Bouř P, Sopková J, Bednarová L, Maloň P, Keiderling TA (1997) Transfer of molecular property tensors in cartesian coordinates: a new algorithm for simulation of vibrational spectra. J Comput Chem 18(5):646–659

Burai R, Ait-Bouziad N, Chiki A, Lashuel HA (2015) Elucidating the role of site-specific nitration of α-synuclein in the pathogenesis of Parkinson’s disease via protein semisynthesis and mutagenesis. J Am Chem Soc 137(15):5041–5052 PubMed

Campolo N, Issoglio FM, Estrin DA, Bartesaghi S, Radi R (2020) 3-Nitrotyrosine and related derivatives in proteins: precursors, radical intermediates and impact in function. Essays Biochem 64(1):111–133 PubMed

Case DA et al (2012) AMBER 12. University of California, San Francisco

Castro L, Demicheli V, Tortora V, Radi R (2011) Mitochondrial protein tyrosine nitration. Free Radic Res 45(1):37–52 PubMed

Chai J-D, Head-Gordon M (2008) Long-range corrected hybrid density functionals with damped atom-atom dispersion corrections. Phys Chem Chem Phys 10(44):6615–6620 PubMed

Cheeseman JR, Frisch MJ, Devlin FJ, Stephens PJ (1996) Ab Initio calculation of atomic axial tensors and vibrational rotational strengths using density functional theory. Chem Phys Lett 252(3–4):211–220

Cho FH, Kuo SC, Lai YH (2017) Surface-plasmon-induced azo coupling reaction between nitro compounds on dendritic silver monitored by surface-enhanced Raman spectroscopy. RSC Adv 7(17):10259–10265

Di Bello C, Griffin JH (1975) Circular dichroism and absorbance properties of nitrotyrosyl chromophores in staphylococcal nuclease and in a model diketopiperazine. J Biol Chem 250:1445–1450 PubMed

Duda JE, Giasson BI, Chen Q, Gur TL, Hurtig HI, Stern MB, Gollomp SM, Ischiropoulos H, Lee VM, Trojanowski JQ (2000) Widespread nitration of pathological inclusions in neurodegenerative synucleinopathies. Am J Pathol 157(5):1439–1445 PubMed PMC

Erickson BW, Merrifield RB (1973) Acid stability of several benzylic protecting groups used in solid-phase peptide synthesis. Rearrangement of O-benzyltyrosine to 3-benzyltyrosine. J Am Chem Soc 95(11):3750–3756 PubMed

Feeney MB, Schöneich Ch (2013) Proteomic approaches to analyze protein tyrosine nitration. Antioxid Redox Signal 19(11):1247–1256 PubMed PMC

Fields GB, Noble RL (1990) Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids. Int J Pept Prot Res 35(3):161–214

Frisch MJ et al (2016) Gaussian 16 revision A.03. Gaussian, Inc., Wallingford CT

Fujiwara H, Hasegawa M, Dohmae N, Kawashima A, Masliah E, Goldberg MS, Shen J, Takio K, Iwatsubo T (2002) Alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol 4:160–164 PubMed

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):985–989 PubMed

Graham D, Thompson DG, Smith WE, Faulds K (2008) Control of enhanced Raman scattering using a DNA-based assembly process of dye-coded nanoparticles. Nat Nanotechnol 3(9):548–551 PubMed

Guerrini L, Graham D (2012) Molecularly-mediated assemblies of plasmonic nanoparticles for Surface-Enhanced Raman spectroscopy applications. Chem Soc Rev 41:7085–7107 PubMed

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):3865–3872 PubMed

Huang YF, Zhu HP, Liu GK, Wu DY, Ren B, Tian ZQ (2010) When the signal is not from the original molecule to be detected: chemical transformation of para-aminothiophenol on Ag during the SERS measurement. J Am Chem Soc 132(27):9244–9246 PubMed

Hudecová J, Horníček J, Buděšínský M, Šebestík J, Šafařík M, Zhang G, Keiderling TA, Bouř P (2012) Three types of induced tryptophan optical activity compared in model dipeptides: theory and experiment. Chem Phys Chem 13(11):2748–2760 PubMed

Ischiropoulos H, Zhu L, Chen J, Tsai M, Martin JC, Smith CD (1992) Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch Biochem Biophys 298(2):431–437 PubMed

Izzo GE, Jordan F, Mendelsohn R (1982) Resonance Raman and 500-MHz

Ježek J, Hlaváček J, Šebestík J (2017) Applications for treatment of neurodegenerative diseases. Prog Drug Res 72:99–134

Jing H, Zhang Q, Large N, Yu C, Blom DA, Nordlander P, Wang H (2014) Tunable plasmonic nanoparticles with catalytically active high-index facets. Nano Lett 14(6):3674–3682 PubMed

Keiderling TA (2020) Structure of condensed phase peptides: insights from vibrational circular dichroism and raman optical activity techniques. Chem Rev 120(7):3381–3419 PubMed

Keiderling TA, Lakhani A (2018) Mini review: Instrumentation for vibrational circular dichroism spetroscopy, still a role for dispersive instruments. Chirality 30(3):238–253 PubMed

Kessler J, Andrushchenko V, Kapitán J, Bouř P (2018) Insight into vibrational circular dichroism of proteins by density functional modeling. Phys Chem Chem Phys 20:4926–4935 PubMed

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 A 2(5):799–805

Kleinman SL, Frontiera RR, Henry AI, Dieringer JA, Van Duyne RP (2013) Creating, characterizing and controlling chemistry with SERS hot spots. Phys Chem Chem Phys 15(1):21–36 PubMed

Krajnik M, Schäfer M, Sobanski P, Kowalewski J, Bloch-Boguslawska E, Zylicz Z, Mousa SA (2010) Enkephalin, its precursor, processing enzymes, and receptor as part of a local opioid network throughout the respiratory system of lung cancer patients. Human Pathol 41(5):632–642

Kurouski D, Van Duyne RP (2015) In situ detection and identification of hair dyes using surface-enhanced Raman spectroscopy (SERS). Anal Chem 87(5):2901–2906 PubMed

Kurouski D, Lee H, Roschangar F, Senanayake Ch (2017) Surface-enhanced raman spectroscopy: from concept to practical application. Spectroscopy 32(11):36–44

Lakhani A, Malon P, Keiderling TA (2009) Comparison of vibrational circular dichroism instruments: development of a new dispersive VCD. Appl Spect 63(7):775–785

Larsen MR, Trelle MB, Thingholm TE, Jensen ON (2006) Analysis of posttranslational modifications of proteins by tandem mass spectrometry. Biotechniques 40(6):790–798 PubMed

Leopold N, Lendl B (2003) A new method for fast preparation of highly surface-enhanced Raman scattering (SERS) active silver colloids at room temperature by reduction of silver nitrate with hydroxylamine hydrochloride. J Phys Chem B 107(24):5723–5727

Marenich AV, Cramer CJ, Truhlar DG (2009) Universal solvation model based on solute electron density and a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. J Phys Chem B 113(18):6378–6396 PubMed

Martins VR, Beraldo FH, Hajj GN, Lopes MH, Lee KS, Linden PMAR (2010) Prion protein: orchestrating neurotrophic activities. Curr Issues Mol Biol 12(2):63–86 PubMed

Martinsson E, Shahjamali MM, Large N, Zaraee N, Schatz GC, Aili D, Mirkin CA (2015) Influence of surfactant bilayers on the refractive index sensitivity and catalytic properties of anisotropic gold nanoparticles. Small 12(3):330–342 PubMed

Meade RM, Fairlie DP, Mason JM (2019) Alpha-synuclein structure and Parkinson’s disease—lessons and emerging principles. Mol Neurodegener 14:1

Mulfinger L, Solomon SD, Bahadory M, Jeyarajasingam AV, Rutkowsky SA, Boritz C (2007) Synthesis and study of silver nanoparticles. J Chem Educ 84(2):322–325

Mulvihill MJ, Ling XY, Henzie J, Yang P (2010) Anisotropic etching of silver nanoparticles for plasmonic structures capable of single-particle SERS. J Am Chem Soc 132(1):268–274 PubMed

Niederhafner P, Šafařík M, Brichtová E, Šebestík J (2016) Rapid acidolysis of benzyl group as a suitable approach for synthesis of peptides naturally produced by oxidative stress and containing 3-nitrotyrosine. Amino Acids 48(4):1087–1098 PubMed

Niederhafner P, Šafařík M, Brichtová E, Šebestík J (2019) Correction to: Rapid acidolysis of benzyl group as a suitable approach for syntheses of peptides naturally produced by oxidative stress and containing 3-nitrotyrosine. Amino Acids 51(10–12):1689–1690 PubMed

Niederhafner P, Brichtová E, Šafařík M, Keiderling TA, Šebestík J (2019b) The role of tyrosine oxidation in structures and properties of neurodegenerative peptides and proteins. In Peptide Science 2018: Proceedings of the 10

Novák V, Šebestík J, Bouř P (2012) Theoretical modeling of the surface-enhanced Raman optical activity. J Chem Theory Comput 8(5):1714–1720 PubMed

Novák V, Dendisová M, Matějka P, Bouř P (2016) Explanation of surface-enhanced raman scattering intensities of p-aminobenzenethiol by density functional computations. J Phys Chem C 120(32):18275–18280

Oueslati A, Fournier M, Lashuel HA (2010) Role of post-translational modifications in modulating of structure, function and toxicity of alpha-synuclein. Implications for Parkinson’s disease pathogenesis and therapies. Progress Brain Res 183(C):115–145

Perdew JP, Burke K, Wang Y (1996) Generalized gradient approximation for the exchange-correlation hole of a many-electron system. Phys Rev B 54(23):16533–16539

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):1605–1612 PubMed

Quaroni L, Smith WE (1999a) Nitration of internal tyrosine of cytochrome c probed by resonance Raman scattering. Biospectroscopy 5:S71–S76 PubMed

Quaroni L, Smith WE (1999b) The Nitro Stretch as a Probe of the Environment of Nitrophenols and Nitrotyrosines. J Raman Spectrosc 30(7):537–542

Radi R (2004) Nitric oxide, oxidants, and protein tyrosine nitration. Proc Natl Acad Sci USA 101(12):4003–4008 PubMed

Radi R (2013) Protein tyrosine nitration: biochemical mechanisms and structural basis of functional effects. Acc Chem Res 46(2):550–559 PubMed

Rahmelow K, Hübner W, Ackermann Th (1998) Infrared absorbances of protein side chains. Anal Biochem 257(1):1–11 PubMed

Rehor I, Cigler P (2014) Precise estimation of HPHT nanodiamond size distribution based on transmission electron microscopy image analysis. Diam Relat Mater 46:21–24

Reynolds MR, Berry RW, Binder LI (2005) Site specific nitration and oxidative dityrosine bridging of the tau protein by peroxynitrite: implications for Alzheimer’s disease. Biochemistry 44(5):1690–1700 PubMed

Ruud K, Thorvaldsen AJ (2009) Theoretical approaches to the calculation of raman optical activity spectra. Chirality 21:E54–E67 PubMed

Rycenga M, Langille MR, Personick ML, Ozel T, Mirkin CA (2012) Chemically isolating hot spots on concave nanocubes. Nano Lett 12(12):6218–6222 PubMed

Rygula A, Majzner K, Marzec KM, Kaczor A, Pilarczyk M, Baranska M (2013) Raman spectroscopy of proteins: a review. J Raman Spectrosc 44(8):1061–1076

Seballos L, Richards N, Stevens DJ, Patel M, Kapitzky L, Lokey S, Millhauser G, Zhang JZ (2007) Competitive binding effects on surface-enhanced Raman scattering of peptide molecules. Chem Phys Lett 447(4–6):335–339 PubMed PMC

Šebestík J, Bouř P (2011) Raman optical activity of methyloxirane gas and liquid. J Phys Chem Lett 2(5):498–502

Šebestík J, Šafařík M, Bouř P (2012) Ferric complexes of 3-hydroxy-4-pyridinones characterized by density functional theory and Raman and UV-vis spectroscopies. Inorg Chem 51(8):4473–4481 PubMed

Shao Z, Zhu W, Wang H, Yang Q, Yang S, Liu X, Wang G (2013) Controllable synthesis of concave nanocubes, right bipyramids, and 5-fold twinned nanorods of palladium and their enhanced electrocatalytic performance. J Phys Chem C 117(27):14289–14294

Sharma B, Frontiera RR, Henry AI, Ringe E, Van Duyne RP (2012) SERS: Material, applications and the future. Mater Today 15(1–2):16–25

Soum E, Brazzolotto X, Goussias C, Bouton C, Moulis J-M, Mattioli TA, Drapier J-C (2003) Peroxynitrite and nitric oxide differently target the iron-sulfur cluster and amino acid residues of human iron regulatory protein 1. Biochemistry 42(25):7648–7654 PubMed

Stamplecoskie KG, Scaiano JC, Tiwari VS, Anis H (2011) Optimal size of silver nanoparticles for surface-enhanced raman spectroscopy. J Phys Chem C 115(5):1403–1409

Stiles PL, Dieringer JA, Shah NC, Van Duyne RP (2008) Surface-enhanced raman spectroscopy. Ann Rev Anal Chem 1(1):601–626

Stuart ChM, Frontiera RR, Mathies RA (2007) Excited-State structure and dynamics of cis- and trans-azobenzene from resonance Raman intensity analysis. J Phys Chem A 111(48):12072–12080 PubMed

Sun M, Xu H (2012) A novel application of plasmonics: plasmon-driven surface-catalyzed reactions. Small 8(18):2777–2786 PubMed

Taylor RW, Lee TC, Scherman OA, Esteban R, Aizpurua J, Huang FM, Baumberg JJ, Mahajan S (2011) Precise subnanometer plasmonic junctions for SERS within gold nanoparticle assemblies using cucurbit [n]uril “glue.” ACS Nano 5(5):3878–3887 PubMed

Tomasi J, Mennucci B, Cammi R (2005) Quantum mechanical continuum solvation models. Chem Rev 105:2999–3093 PubMed

Tsikas D, Duncan MW (2014) Mass spectrometry and 3-nitrotyrosine: Strategies, controversies, and our current perspective. Mass Spectrom Rev 33(4):237–276 PubMed

Tuma R (2005) Raman spectroscopy of proteins: from peptides to large assemblies. J Raman Spectrosc 36(4):307–319

Ulmer TS, Bax A, Cole NB, Nussbaum RL (2005) Structure and dynamics of micelle bound human alpha-synuclein. J Biol Chem 280:9595–9603 PubMed

Valim LR, Davis JA, Jensen KT, Guo R, Willison KR, Spickett CM, Pitt AR, Klug DR (2014) Identification and relative quantification of tyrosine nitration in a model peptide using two-dimensional infrared spectroscopy. J Phys Chem B 118(45):12855–12864

Vana L, Kanaan NM, Hakala K, Weintraub ST, Binder LI (2011) Peroxynitrite-induced nitrative and oxidative modifications alter tau filament formation. Biochemistry 50(7):1203–1212 PubMed PMC

Venyaminov SYu, Kalnin NN (1990) Quantitative IR spectrophotometry of peptide compounds in water (H2O) Solutions. I. spectral parameters of amino acid residue absorption bands. Biopolymers 30(13–14):1243–1257 PubMed

Woody AY, Woody RW (2003) Individual tyrosine side-chain contributions to circular dichroism of ribonuclease. Biopolymers 72(6):500–513 PubMed

Yamamoto S, Bouř P (2013) Transition polarizability model of induced resonance Raman optical activity. J Comput Chem 34(25):2152–2158 PubMed

Yamashiro D, Li CH (1973) Adrenocorticotropins 44 Total synthesis of the human hormone by the solid-phase method. J Am Chem Soc 95(4):1310–1315 PubMed

Yanai T, Tew D, Handy N (2004) A new hybrid exchange-correlation functional using the Coulomb-attenuating method (CAM-B3LYP). Chem Phys Lett 393(1–3):51–57

Yttenberg AJ, Jensen ON (2010) Modification-specific proteomics in plant biology. J Proteomics 73(11):2249–2266

Zahn R, Liu A, Lührs T, Riek R, von Schroetter Ch, García FL, Billeter M, Calzolai L, Wider G, Wüthrich K (2000) NMR solution structure of the human prion protein. Proc Natl Acad Sci USA 97(1):145–150 PubMed

Zhang Q, Large N, Nordlander P, Wang H (2014) Porous Au nanoparticles with tunable plasmon resonances and intense field enhancements for single-particle SERS. J Phys Chem Lett 5(2):370–374 PubMed

Zhang Q, Large N, Wang H (2014) Gold nanoparticles with tipped surface structures as substrates for single-particle surface-enhanced Raman spectroscopy: concave nanocubes, nanotrisoctahedra, and nanostars. ACS Appl Mater Interf 6(19):17255–17267

Zhao Y, Truhlar DG (2008) The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor Chem Acc 120(1–3):215–241

Zhao Y, Zhang Y, Sun H, Maroto R, Brasier AR (2017) Selective affinity enrichment of nitrotyrosine-containing peptides for quantitative analysis in complex samples. J Proteome Res 16(8):2983–2992 PubMed PMC

Zhao J, Wu J, Yang Z, Ouyang L, Zhu L, Gao Z, Hailing Li (2019) Nitration of hIAPP promotes its toxic oligomer formation and exacerbates its toxicity towards INS-1 cells. Nitric Oxide 87:23–30 PubMed

Photochemical synthesis of pink silver and its use for monitoring peptide nitration via surface enhanced Raman spectroscopy (SERS)