?-Sheet structure formation of proteins in solid state as revealed by circular dichroism spectroscopy

Hu, Hongyu; Li, Qi; Cheng, Hongchang; Du, Hai-Ning

doi:10.1002/1097-0282(2001)62:1<15::aid-bip30>3.0.co;2-j

Cited by 67 publications

(36 citation statements)

References 28 publications

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“…4,6,7) The method is often used in freeze-dried protein formulation studies since the resolution enhancement of amide I absorption (self-deconvolution and second derivative) allows comparison of protein conformation in diverse environments. Whereas the dehydration-induced conformation changes has been supported by other analytical methods (e.g., solid circular dichroism), 29) there are some debates on the sample preparation and data interpretation (e.g., band assignment) of the dried protein FT-IR analysis.…”

Section: Discussionmentioning

confidence: 94%

Protection of Protein Secondary Structure by Saccharides of Different Molecular Weights during Freeze-Drying

Izutsu

Aoyagi

Kojima

2004

CHEMICAL & PHARMACEUTICAL BULLETIN

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Development of recombinant therapeutic proteins requires rational design of both the formulations and manufacturing processes. [1][2][3][4][5] Freeze-drying is a popular method to retain long-term stability of various proteins that are not sufficiently stable in aqueous solutions, although the stresses incurred during the freeze-drying process often induce partial unfolding and resulting protein aggregation in the rehydrated solutions. [6][7][8] Stable formulation design is required to avoid the biological activity loss and possible immunogenic effect of the structurally and/or chemically altered protein molecules.Many polyols (e.g., saccharides and sugar alcohols) protect proteins from inactivation during freeze-drying and subsequent storage. They protect native protein conformation against dehydration stresses by replacing essential water molecules through molecular interaction (e.g., hydrogen bonding) with the protein molecules.1-4,9) Some polyols also improve the physical and chemical stability of proteins during the freeze-drying process and subsequent storage by keeping the protein within a highly viscose glass-state amorphous solid with limited molecular mobility. 10,11) The choice of an appropriate saccharide and/or saccharide combination is crucial to the formulation design.1,2,12) Sucrose has been added to many freeze-drying formulations because of its potent structure-stabilizing effect and proven safety, whereas the low glass transition temperatures of the sucrose-based amorphous freeze-dried solids result in stability problems in storage at higher temperature or higher humidity. 13) Various saccharides posses different physical properties and protein-stabilizing effects.1-3) Large saccharide molecules often provide freeze-dried solids with high glass transition temperatures (T g s), which are suitable for protein storage stability. In contrast, they often show smaller effect to protect lower concentration enzymes (e.g., 1 mg/ml catalase) from inactivation during freeze-drying. 14)Protein molecules face different stresses during the freezedrying process depending on the initial concentrations, whereas the relationship between the saccharide molecular weights and the protein-stabilizing effect in freeze-drying of pharmaceutically relevant, high concentration (e.g., greater than 1 mg/ml) protein solutions has not been well elucidated.In addition to the low temperature and dehydration stresses, which are independent of the initial protein concentrations, lower concentration proteins are more likely to undergo physical stress on ice, air, and container surfaces. 3,4,15) In the present work, we used Fourier transform infrared (FT-IR) spectroscopy to study the effects of saccharides with different molecular weights on the secondary structure of proteins (BSA, ovalbumin) freeze-dried in high concentration. Addition of sodium tetraborate (Na 2 B 4 O 7 , borax) to aqueous saccharide solutions raises the "effective" saccharide molecular size through complex formation between a tetrahydroxy borate ion and one o...

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Section: Discussionmentioning

confidence: 94%

Protection of Protein Secondary Structure by Saccharides of Different Molecular Weights during Freeze-Drying

Izutsu

Aoyagi

Kojima

2004

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…5C). We also recorded the CD spectra in solid state to characterize the secondary structures of these peptides under amyloid conditions (40). The solid-state CD spectrum of TDP(311-360) shows a negative peak at 225 nm and a strong positive peak at 196 nm, suggesting that this peptide also forms a ␤-sheet-rich structure in the solid amyloid form (Fig.…”

Section: Aggregation Of Tdp-43 and Its Fragments In Vitro-mentioning

confidence: 99%

Structural Transformation of the Amyloidogenic Core Region of TDP-43 Protein Initiates Its Aggregation and Cytoplasmic Inclusion

Jiang

Xia

Zhao

et al. 2013

Journal of Biological Chemistry

Self Cite

140

190

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Background:The highly flexible C-terminal region of TDP-43 is implicated in disease pathology. Results: An amyloidogenic core was identified to be critical for TDP-43 aggregation. Conclusion: Helix-to-sheet structural transformation of the amyloidogenic core initiates TDP-43 aggregation and cytoplasmic inclusion formation. Significance: This is a potential therapeutic target for mitigating the TDP-43 proteinopathies.

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“…85 More recently a-helix-bundle proteins have been studied as LB films (and in solution). 86 Surface pressure effects in LB protein films were studied by CD and other techniques by Nicolini et al 87 A tendency to increase b-sheet structure in proteins' films dried on a thin quartz window compared to solution phase samples was observed by Hu et al, 88 whose results were however criticized by Harada and Kuroda 89 using the dedicated J-800KCM instrument. 10 Nakagawa et al studied amino acid films prepared with vacuum sublimation technique.…”

Section: Filmsmentioning

confidence: 99%

Experimental aspects of solid state circular dichroism

2009

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?-Sheet structure formation of proteins in solid state as revealed by circular dichroism spectroscopy

Cited by 67 publications

References 28 publications

Protection of Protein Secondary Structure by Saccharides of Different Molecular Weights during Freeze-Drying

Protection of Protein Secondary Structure by Saccharides of Different Molecular Weights during Freeze-Drying

Structural Transformation of the Amyloidogenic Core Region of TDP-43 Protein Initiates Its Aggregation and Cytoplasmic Inclusion

Experimental aspects of solid state circular dichroism

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