Solid state chemistry of proteins IV. what is the meaning of thermal denaturation in freeze dried proteins?

Pikal, Michael J.; Rigsbee, Daniel R.; Akers, Michael J.

doi:10.1002/jps.21517

Cited by 9 publications

(6 citation statements)

References 18 publications

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“…Therefore, the T g in dry proteins is estimated by extrapolation of DSC data of excipient (e.g., disaccharides) and protein mixtures. Consistent in the literature is furthermore that proteins in the solid state show an irreversible denaturation, in most cases well above 100 °C, which is assumed to only take place after the glass transition and is seen in the DSC as an endotherm . Its corresponding temperature is sometimes referred to as the apparent denaturation temperature …”

Section: Resultsmentioning

confidence: 91%

“…Consistent in the literature is furthermore that proteins in the solid state show an irreversible denaturation, in most cases well above 100 °C, which is assumed to only take place after the glass transition and is seen in the DSC as an endotherm. 54 Its corresponding temperature is sometimes referred to as the apparent denaturation temperature. 49 A comparison of MTA-F (direct triplicate) and DSC data of lysozyme is given in Figure 7a.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Ultrasensitive Microstring Resonators for Solid State Thermomechanical Analysis of Small and Large Molecules

et al. 2018

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Section: Resultsmentioning

confidence: 91%

Section: ■ Results and Discussionmentioning

confidence: 99%

Ultrasensitive Microstring Resonators for Solid State Thermomechanical Analysis of Small and Large Molecules

et al. 2018

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“…For the most part, the reported denaturation temperatures for dried proteins are quite high, often above 150°C (285)(286)(287). The T m value, like the T g value, appears to scale with moisture content and with each other (287)(288)(289). A detailed discussion of how freeze-dried proteins denature has recently been published (288,290), as it relates to T g and other glassy state behavior.…”

Section: Denaturation In the Solid Statementioning

confidence: 96%

“…The T m value, like the T g value, appears to scale with moisture content and with each other (287)(288)(289). A detailed discussion of how freeze-dried proteins denature has recently been published (288,290), as it relates to T g and other glassy state behavior. For example, for hGH, the denaturation only occurs above T g , is cooperative and is mostly irreversible (290).…”

Section: Denaturation In the Solid Statementioning

confidence: 98%

Stability of Protein Pharmaceuticals: An Update

Manning¹,

Chou²,

Murphy³

et al. 2010

Pharm Res

986

782

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In 1989, Manning, Patel, and Borchardt wrote a review of protein stability (Manning et al., Pharm. Res. 6:903-918, 1989), which has been widely referenced ever since. At the time, recombinant protein therapy was still in its infancy. This review summarizes the advances that have been made since then regarding protein stabilization and formulation. In addition to a discussion of the current understanding of chemical and physical instability, sections are included on stabilization in aqueous solution and the dried state, the use of chemical modification and mutagenesis to improve stability, and the interrelationship between chemical and physical instability.

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“…Alternatively, modulated DSC techniques, using oscillating heating rates, can resolve overlapping thermal events in protein isolates . Modulated DSC and simulations of human growth hormone unfolding suggested that dried proteins are thermodynamically unstable, even when formulated with excipients, such as disaccharides, and that kinetic limitations, such as low mobility, are what prevent their spontaneous unfolding . This is again consistent with denaturing being constrained below T g .…”

Section: The Amorphous Phasementioning

confidence: 99%

Thermal Transitions and Structural Relaxations in Protein‐Based Thermoplastics

Bier

Verbeek

Lay

2013

Macro Materials & Eng

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Protein‐based thermoplastics resemble semi‐crystalline polymers, suggesting the occurrence of a glass transition (Tg) and melting point. Denaturing a protein's native structure is often called melting, but this does not necessarily imply complete unfolding into a fully amorphous structure as true melting would. Protein secondary structures, such as α‐helices and β‐sheets, can remain after denaturing, stay intact above the Tg and do not necessarily melt at typical processing temperatures. This implies that consolidation of aggregated protein particles into a macroscopically monolithic material depends on inter‐chain interactions in the amorphous phase and on newly formed secondary structures. Structural relaxations and transition temperatures of the amorphous phase are influenced and constrained by the presence of these secondary structures as well as heavily influenced by plasticizers.

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Solid state chemistry of proteins IV. what is the meaning of thermal denaturation in freeze dried proteins?

Cited by 9 publications

References 18 publications

Ultrasensitive Microstring Resonators for Solid State Thermomechanical Analysis of Small and Large Molecules

Ultrasensitive Microstring Resonators for Solid State Thermomechanical Analysis of Small and Large Molecules

Stability of Protein Pharmaceuticals: An Update

Thermal Transitions and Structural Relaxations in Protein‐Based Thermoplastics

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