Use of Raman and Raman optical activity for the structural characterization of a therapeutic monoclonal antibody formulation subjected to heat stress

Thiagarajan, Geetha; Widjaja, Effendi; Heo, Jun Hyuk; Cheung, Jason K.; Wabuyele, Busolo Wa; Mou, Xiaodun; Shameem, Mohammed

doi:10.1002/jrs.4679

Cited by 27 publications

(19 citation statements)

References 31 publications

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“…2,7 Especially the chiroptical variant of Raman spectroscopy, Raman optical activity (ROA), is very sensitive to the three-dimensional solution structure and dynamics of biomolecules. 8,9 It has been applied to study the solution structure of peptides [10][11][12] , proteins [13][14][15] , glycoproteins [16][17][18] , complex sugars 19 and even intact viruses [20][21][22] . While the unique conformational sensitivity of ROA is recognised, the biggest challenge lies in the detailed interpretation of the experimental ROA patterns.…”

Section: Introductionmentioning

confidence: 99%

Ramachandran mapping of peptide conformation using a large database of computed Raman and Raman optical activity spectra

Mensch

Barron

Johannessen

2016

Phys. Chem. Chem. Phys.

136

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The past decades, Raman optical activity (ROA) spectroscopy has been shown to be very sensitive to the solution structure of peptides and proteins. A major and urgent challenge remains the need to make detailed assignments of experimental ROA patterns and relate those to the solution structure adopted by the protein. The past years, theoretical developments and implementations of ROA theory have made it possible to use quantum chemical methods to compute ROA spectra of peptides. In this work, a large database of ROA spectra of peptide model structures describing the allowed backbone conformations of proteins were systematically calculated and used to make unprecedented detailed assignments of experimental ROA patterns to the conformational elements of the peptide in solution. By using a similarity index to compare an experimental spectrum to the database spectra (2902 theoretical spectra), the conformational preference of the peptide in solution can be assigned to a very specific region in the Ramachandran space. For six (poly)peptides this approach was validated and gives excellent agreement between experiment and theory. Additionally, hydrogen/deuterium exchanged structures and the conformational dependence of the amide modes in Raman spectra can be analysed using the new database. The excellent agreement between experiment and theory demonstrates the power of the newly developed database as a tool to study Raman and ROA patterns of peptides and proteins. The interpretation of experimental ROA patterns of different proteins published in scientific literature is discussed based on the spectral trends observed in the database.

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Section: Introductionmentioning

confidence: 99%

Ramachandran mapping of peptide conformation using a large database of computed Raman and Raman optical activity spectra

Mensch

Barron

Johannessen

2016

Phys. Chem. Chem. Phys.

136

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“…More recently, unique sensitivity of ROA was reported by researchers at Merck for the onset of spectral changes due to structural instability of monoclonal antibody formulations during heat stress. Changes in the ROA were observed after only 1 week, whereas changes were not seen in ECD, Raman, or intrinsic fluorescence until after 3 weeks . Apparently, ROA is more sensitive to the stereo‐structural at the higher‐order level of biopharmaceuticals whereas more conventional spectroscopic techniques were only able to report changes in the secondary structure which did not occur until later.…”

Section: Future Development and Challenges For Voamentioning

confidence: 95%

Vibrational optical activity: From discovery and development to future challenges

Nafie

2020

Chirality

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Vibrational optical activity (VOA) consisting of infrared vibrational circular dichroism (VCD) and vibrational Raman optical activity (ROA) was predicted, discovered, and confirmed between 1971 and 1975. My path to VOA was mentored by three pioneers of chirality and vibrational spectroscopy: Professors Albert Moscowitz, Warner L. Peticolas, and Philip J. Stephens, and while they are no longer alive today, the Chirality Medal, my award address, and this paper are dedicated to each of them. Since the discovery of VOA, a number of key advances have made possible the current era of widespread applications. The principal instrumental advances were Fourier-transform VCD (FT-VCD) and multichannel charge coupled detector (CCD) ROA. Computational advances include the first complete quantum chemistry formulation of VCD leading to the magnetic field perturbation (MFP) and the nuclear velocity perturbation (NVP) theories. The strength of VOA is the comparison between measured and calculated spectra that enables the determination of absolute configuration and solution-state conformations. More recently, VCD has uncovered supramolecular chirality in amyloid fibrils and ROA to high-order protein structure. Future challenges for VOA include describing the effects of weak intermolecular interactions, transfer of chirality, solvent effects, supramolecular chirality, and the generation of nuclear velocity electron current density. K E Y W O R D S vibrational circular dichroism (VCD), Raman optical activity (ROA)

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“…A recently published example was the use of ROA for the structural characterization of a monoclonal antibody subjected to heat stress [97]. Now that patent protection is expiring on the first tranche of biopharmaceuticals, companies are working to produce 'biosimilars' which reproduce the overall structure, function and clinical characteristics of the original product.…”

Section: Future Directionsmentioning

confidence: 99%

The development of biomolecular Raman optical activity spectroscopy

Barron

2015

BSI

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Abstract. Following its first observation over 40 years ago, Raman optical activity (ROA), which may be measured as a small difference in the intensity of vibrational Raman scattering from chiral molecules in right-and left-circularly polarized incident light or, equivalently, the intensity of a small circularly polarized component in the scattered light using incident light of fixed polarization, has evolved into a powerful chiroptical spectroscopy for studying a large range of biomolecules in aqueous solution. The long and tortuous path leading to the first observations of ROA in biomolecules in 1989, in which the author was closely involved from the very beginning, is documented, followed by a survey of subsequent developments and applications up to the present day. Among other things, ROA provides information about motif and fold, as well as secondary structure, of proteins; solution structure of carbohydrates; polypeptide and carbohydrate structure of intact glycoproteins; new insight into structural elements present in unfolded protein sequences; and protein and nucleic acid structure of intact viruses. Quantum chemical simulations of observed Raman optical activity spectra provide the complete three-dimensional structure, together with information about conformational dynamics, of smaller biomolecules. Biomolecular ROA measurements are now routine thanks to a commercial instrument based on a novel design becoming available in 2004.

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Use of Raman and Raman optical activity for the structural characterization of a therapeutic monoclonal antibody formulation subjected to heat stress

Cited by 27 publications

References 31 publications

Ramachandran mapping of peptide conformation using a large database of computed Raman and Raman optical activity spectra

Ramachandran mapping of peptide conformation using a large database of computed Raman and Raman optical activity spectra

Vibrational optical activity: From discovery and development to future challenges

The development of biomolecular Raman optical activity spectroscopy

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