Raman spectroscopy of protein pharmaceuticals.

Recent advances in optical and spectroscopic technologies have enabled a plethora of Raman spectrometers that are suitable for studies of protein pharmaceuticals. Highly sensitive Raman spectrometers have overcome the handicap of the fundamentally weak Raman effect that hampered their applications to protein pharmaceuticals in the past. These Raman spectrometers can now routinely measure protein therapeutics at the low concentration of 1 mg/mL, which is on par with other spectroscopic methods such as CD, fluorescence and FTIR spectroscopies. In this article, various Raman techniques that can be used for protein pharmaceutical studies are reviewed. Novel Raman marker of proteins discovered from fundamental studies of protein complexes are examined along with established Raman spectra and structure correlations. Examples of Raman spectroscopic studies of protein pharmaceuticals are demonstrated. Future applications of Raman spectroscopy to protein pharmaceuticals are discussed.

[1]  J. King,et al.  Distinct cysteine sulfhydryl environments detected by analysis of Raman S-hh markers of Cys-->Ser mutant proteins. , 2001, Journal of molecular biology.

[2]  R. Schweitzer-Stenner,et al.  Visible and UV-resonance Raman spectroscopy of model peptides , 2001 .

[3]  S. Asher,et al.  UV resonance Raman spectroscopy for analytical, physical, and biophysical chemistry. Part 2. , 1993, Analytical chemistry.

[4]  P. Carey,et al.  Proteins can convert to β‐sheet in single crystals , 2004 .

[5]  J. Rabolt,et al.  Fourier transform Raman spectroscopy : from concept to experiment , 1994 .

[6]  G. Thomas,et al.  Demonstration by ultraviolet resonance Raman spectroscopy of differences in DNA organization and interactions in filamentous viruses Pf1 and fd. , 1999, Biochemistry.

[7]  A. Cooper,et al.  Vibrational Raman optical activity of alpha-lactalbumin: comparison with lysozyme, and evidence for native tertiary folds in molten globule states. , 1995, Journal of molecular biology.

[8]  Michael W. Blades,et al.  The power distribution advantage of fiber-optic coupled ultraviolet resonance Raman spectroscopy for bioanalytical and biomedical applications , 2002 .

[9]  R. Dasari,et al.  Ultrasensitive chemical analysis by Raman spectroscopy. , 1999, Chemical reviews.

[10]  Rita L. Wong,et al.  Raman spectroscopic characterization of drying-induced structural changes in a therapeutic antibody: correlating structural changes with long-term stability. , 2004, Journal of pharmaceutical sciences.

[11]  Laurence D. Barron,et al.  Molecular Light Scattering and Optical Activity: Second Edition, revised and enlarged , 1983 .

[12]  J. Janesick,et al.  Scientific Charge-Coupled Devices , 2001 .

[13]  G J Thomas,et al.  Structure and organization of bacteriophage Pf3 probed by Raman and ultraviolet resonance Raman spectroscopy. , 2001, Biochemistry.

[14]  R. S. Krishnan,et al.  Raman effect: History of the discovery , 1981 .

[15]  S. Asher,et al.  Dihedral psi angle dependence of the amide III vibration: a uniquely sensitive UV resonance Raman secondary structural probe. , 2001, Journal of the American Chemical Society.

[16]  R. Tuma Raman spectroscopy of proteins: from peptides to large assemblies , 2005 .

[17]  R. McCreery,et al.  Noninvasive identification of materials inside USP vials with Raman spectroscopy and a Raman spectral library. , 1998, Journal of pharmaceutical sciences.

[18]  Steven R. Emory,et al.  Probing Single Molecules and Single Nanoparticles by Surface-Enhanced Raman Scattering , 1997, Science.

[19]  L. Barron,et al.  Vibrational Raman optical activity of monosaccharides , 1993 .

[20]  S. Asher,et al.  UV resonance Raman determination of protein acid denaturation: selective unfolding of helical segments of horse myoglobin. , 1998, Biochemistry.

[21]  Michael D. Morris,et al.  Principles and spectroscopic applications of volume holographic optics , 1993 .

[22]  B. Brandhuber,et al.  X-ray structure of interleukin-1 receptor antagonist at 2.0-A resolution. , 1995, The Journal of biological chemistry.

[23]  C. Fagnano,et al.  Raman spectroscopic study of the avidin—biotin complex , 1995 .

[24]  T. Shimanouchi,et al.  Interpretation of the doublet at 850 and 830 cm-1 in the Raman spectra of tyrosyl residues in proteins and certain model compounds. , 1975, Biochemistry.

[25]  L. Barron,et al.  Raman optical activity instrument for biochemical studies , 1992 .

[26]  Kun Huang,et al.  Structure-specific effects of protein topology on cross-beta assembly: studies of insulin fibrillation. , 2006, Biochemistry.

[27]  A. Pevsner,et al.  Time-resolved absorption and UV resonance Raman spectra reveal stepwise formation of T quaternary contacts in the allosteric pathway of hemoglobin. , 2004, Journal of molecular biology.

[28]  L. A. Day,et al.  Tryptophan absolute stereochemistry in viral coat proteins from raman optical activity. , 2001, Journal of the American Chemical Society.

[29]  L. Barron,et al.  Raman optical activity characterization of native and molten globule states of equine lysozyme: comparison with hen lysozyme and bovine alpha-lactalbumin. , 2000, Biopolymers.

[30]  H. Sugeta Normal vibrations and molecular conformations of dialkyl disulfides , 1975 .

[31]  Ronald W. Barrett,et al.  Refined crystal structure of the interleukin-1 receptor antagonist. Presence of a disulfide link and a cis-proline. , 1995, European journal of biochemistry.

[32]  Hideo Takeuchi,et al.  Tryptophan Raman bands sensitive to hydrogen bonding and side-chain conformation , 1989 .

[33]  Michael J. Pelletier,et al.  Analytical Applications of Raman Spectroscopy , 1999 .

[34]  M. Weiss,et al.  Mechanism of Insulin Fibrillation , 2004, Journal of Biological Chemistry.

[35]  G. Thomas,et al.  Orientation and interactions of an essential tryptophan (Trp-38) in the capsid subunit of Pf3 filamentous virus. , 2003, Biophysical journal.

[36]  L. Nafie,et al.  Scattered circular polarization Raman optical activity , 1988 .

[37]  G. Thomas,et al.  Studies of virus structure by Raman spectroscopy. Cysteine conformation and sulfhydryl interactions in proteins and viruses. 1. Correlation of the Raman sulfur-hydrogen band with hydrogen bonding and intramolecular geometry in model compounds , 1991 .

[38]  P. Carey,et al.  Following ligand binding and ligand reactions in proteins via Raman crystallography. , 2004, Biochemistry.

[39]  J. Carpenter,et al.  Application of infrared spectroscopy to development of stable lyophilized protein formulations. , 1998, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[40]  G. Thomas,et al.  Structural studies of viruses by laser Raman spectroscopy. Part XXXVI. Cysteine conformation and sulfhydryl interactions in proteins and viruses. 2. Normal coordinate analysis of the cysteine side chain in model compounds , 1992 .

[41]  Jian Dong,et al.  Insulin assembly damps conformational fluctuations: Raman analysis of amide I linewidths in native states and fibrils. , 2003, Journal of molecular biology.

[42]  X. Xie,et al.  Coherent Anti-Stokes Raman Scattering Microscopy: Instrumentation, Theory, and Applications , 2004 .

[43]  W. Hug,et al.  A novel high-throughput Raman spectrometer for polarization difference measurements , 1999 .

[44]  T. Miyazawa,et al.  S–S AND C–S STRETCHING VIBRATIONS AND MOLECULAR CONFORMATIONS OF DIALKYL DISULFIDES AND CYSTINE , 1972 .

[45]  S. Asher,et al.  UV Raman Determination of the Environment and Solvent Exposure of Tyr and Trp Residues , 1998 .

[46]  Lutz Hecht,et al.  Raman optical activity of proteins, carbohydrates and glycoproteins. , 2006, Chirality.

[47]  J. L. McHale Fermi resonance of tyrosine and related compounds. Analysis of the Raman doublet , 1982 .

[48]  J. King,et al.  Disulphide-bonded intermediate on the folding and assembly pathway of a non-disulphide bonded protein , 1997, Nature Structural Biology.

[49]  G. Thomas,et al.  Tyrosine Raman signatures of the filamentous virus Ff are diagnostic of non-hydrogen-bonded phenoxyls: demonstration by Raman and infrared spectroscopy of p-cresol vapor. , 2001, Biochemistry.

[50]  J. Chalmers,et al.  Handbook of vibrational spectroscopy , 2002 .

[51]  Thomas G. Spiro,et al.  Resonance enhancement in the ultraviolet Raman spectra of aromatic amino acids , 1985 .

[52]  D. A. Dougherty,et al.  The Cationminus signpi Interaction. , 1997, Chemical reviews.

[53]  S. Asher,et al.  UVRR spectroscopic studies of valinomycin complex formation in different solvents. , 2005, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[54]  I. Harada,et al.  Normal coordinate analysis of the indole ring , 1986 .

[55]  R. Tuma,et al.  Raman Spectroscopy of Viruses , 2006 .

[56]  P. Carey,et al.  Proinsulin Is Refractory to Protein Fibrillation , 2005, Journal of Biological Chemistry.

[57]  M. Storrie-Lombardi,et al.  Hollow cathode ion lasers for deep ultraviolet Raman spectroscopy and fluorescence imaging , 2001 .

[58]  R. Tuma,et al.  Cysteine conformation and sulfhydryl interactions in proteins and viruses. 3. Quantitative measurement of the Raman S-H band intensity and frequency. , 1993, Biophysical journal.

[59]  H. Scheraga,et al.  Disulfide bond dihedral angles from Raman spectroscopy. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[60]  T. Arakawa,et al.  Changes in protein conformation and dynamics upon complex formation of brain-derived neurotrophic factor and its receptor: investigation by isotope-edited Fourier transform IR spectroscopy. , 2002, Biopolymers.

[61]  S. Asher,et al.  Ultraviolet resonance Raman examination of horse apomyoglobin acid unfolding intermediates. , 1999, Biochemistry.

[62]  D. A. Dougherty,et al.  Cation-π interactions in structural biology , 1999 .

[63]  R. Williams Protein secondary structure analysis using Raman amide I and amide III spectra. , 1986, Methods in enzymology.

[64]  H. Scheraga,et al.  Agreement with the disulfide stretching frequency-conformation correlation of Sugeta, Go, and Miyazawa. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[65]  Wen,et al.  Ultraviolet-resonance raman spectroscopy of the filamentous virus pf3: interactions of trp 38 specific to the assembled virion subunit , 2000, Biochemistry.

[66]  G. Thomas,et al.  Structural studies of viruses by Raman spectroscopy. Novel vibrational assignments for proteins from Raman spectra of viruses , 1998 .

[67]  Todd M. Przybycien,et al.  Secondary structure characterization of beta-lactamase inclusion bodies. , 1994, Protein engineering.

[68]  G. Thomas Raman spectroscopy of protein and nucleic acid assemblies. , 1999, Annual review of biophysics and biomolecular structure.

[69]  Michael D. Morris,et al.  Microscopic and Spectroscopic Imaging of the Chemical State , 1993 .

[70]  E. Blanch,et al.  Raman optical activity comes of age , 2004 .

[71]  J. Bandekar,et al.  Vibrational spectroscopy and conformation of peptides, polypeptides, and proteins. , 1986, Advances in protein chemistry.

[72]  Vibrational Spectra and Molecular Conformations of Dialkyl Disulfides , 1973 .

[73]  D. A. Dougherty,et al.  Cation-π Interactions in Chemistry and Biology: A New View of Benzene, Phe, Tyr, and Trp , 1996, Science.

[74]  Bruce A. Garett Molecular Light Scattering and Optical Activity, 2nd ed , 2005 .

[75]  Richard L. McCreery,et al.  Raman Spectroscopy for Chemical Analysis , 2000 .

[76]  R. Tuma,et al.  Solution conformation of the extracellular domain of the human tumor necrosis factor receptor probed by Raman and UV-resonance Raman spectroscopy: structural effects of an engineered PEG linker. , 1995, Biochemistry.

[77]  G. Thomas,et al.  Structure similarity, difference and variability in the filamentous viruses fd, If1, IKe, Pf1 and Xf. Investigation by laser Raman spectroscopy. , 1983, Journal of molecular biology.

[78]  Robert C. Thompson,et al.  Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor , 1990, Nature.

[79]  C. Ho,et al.  Role of Interhelical H-Bonds (Wα14−Tα67 and Wβ15−Sβ72) in the Hemoglobin Allosteric Reaction Path Evaluated by UV Resonance Raman Spectroscopy of Site-Mutants , 1999 .

[80]  G. Thomas,et al.  UV resonance Raman spectroscopy of DNA and protein constituents of viruses: assignments and cross sections for excitations at 257, 244, 238, and 229 nm. , 1998, Biopolymers.

[81]  I. Harada,et al.  Origin of the doublet at 1360 and 1340 cm -1 in the Raman spectra of tryptophan and related compounds , 1986 .

[82]  S. Asher,et al.  Ultraviolet resonance Raman excitation profiles of tyrosine: dependence of Raman cross sections on excited-state intermediates , 1988 .

[83]  Anthony T. Tu,et al.  Raman spectroscopy in biology: Principles and applications , 1982 .

[84]  Michael S. Feld,et al.  SURFACE-ENHANCED RAMAN SCATTERING : A NEW TOOL FOR BIOMEDICAL SPECTROSCOPY , 1999 .

[85]  G. Thomas,et al.  Structure and interactions of the single-stranded DNA genome of filamentous virus fd: investigation by ultraviolet resonance raman spectroscopy. , 1997, Biochemistry.

[86]  Paul R. Carey,et al.  Biochemical Applications of Raman and Resonance Raman Spectroscopies , 1982 .

[87]  L. Barron,et al.  Raman optical activity instrument for studies of biopolymer structure and dynamics , 1999 .

[88]  T. Spiro,et al.  Protein structure from ultraviolet resonance Raman spectroscopy. , 1993, Methods in enzymology.

[89]  P. Carey,et al.  Raman crystallography and other biochemical applications of Raman microscopy. , 2006, Annual review of physical chemistry.

[90]  Hideo Takeuchi,et al.  Binding mode of Congo Red to Alzheimer's amyloid ?-peptide studied by UV Raman spectroscopy , 2002 .

[91]  T. Arakawa,et al.  Effect of the intermolecular disulfide bond on the conformation and stability of glial cell line-derived neurotrophic factor. , 2002, Protein engineering.

[92]  Bruce A Kerwin,et al.  Anion binding and controlled aggregation of human interleukin-1 receptor antagonist. , 2005, Biochemistry.

[93]  Sanford A. Asher,et al.  UV resonance Raman excitation profiles of the aromatic amino acids , 1986 .