Opposite Effects of Polyols on Antibody Aggregation: Thermal Versus Mechanical Stresses

Abbas, Shermeen A.; Sharma, Vikas; Patapoff, Thomas W.; Kalonia, Devendra S.

doi:10.1007/s11095-011-0593-4

Cited by 25 publications

(13 citation statements)

References 42 publications

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“…This result is consistent with earlier reports, showing that polyols are excellent protein stabilizers [34]. Yet, their stabilizing effect cannot be fully generalized because ethylene glycol has also been reported as thermal destabilizer [35]. Among the other studied co‐solvents, the least deleterious to catalytic activities of DbjA, DhaA, and LinB was DMSO, followed by methanol and DMF, whereas co‐solvents with hydrophobicity parameter log P higher than –0.35 (especially THF, 1,4‐dioxane and acetonitrile) were weakly tolerated (Supporting information, Table S4 and Fig.…”

Section: Resultssupporting

confidence: 93%

Organic co‐solvents affect activity, stability and enantioselectivity of haloalkane dehalogenases

Štěpánková

Damborský

Chaloupková

2013

Biotechnology Journal

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Haloalkane dehalogenases are microbial enzymes with a wide range of biotechnological applications, including biocatalysis. The use of organic co-solvents to solubilize their hydrophobic substrates is often necessary. In order to choose the most compatible co-solvent, the effects of 14 co-solvents on activity, stability and enantioselectivity of three model enzymes, DbjA, DhaA, and LinB, were evaluated. All co-solvents caused at high concentration loss of activity and conformational changes. The highest inactivation was induced by tetrahydrofuran, while more hydrophilic co-solvents, such as ethylene glycol and dimethyl sulfoxide, were better tolerated. The effects of co-solvents at low concentration were different for each enzyme-solvent pair. An increase in DbjA activity was induced by the majority of organic co-solvents tested, while activities of DhaA and LinB decreased at comparable concentrations of the same co-solvent. Moreover, a high increase of DbjA enantioselectivity was observed. Ethylene glycol and 1,4-dioxane were shown to have the most positive impact on the enantioselectivity. The favorable influence of these co-solvents on both activity and enantioselectivity makes DbjA suitable for biocatalytic applications. This study represents the first investigation of the effects of organic co-solvents on the biocatalytic performance of haloalkane dehalogenases and will pave the way for their broader use in industrial processes.

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Section: Resultssupporting

confidence: 93%

Organic co‐solvents affect activity, stability and enantioselectivity of haloalkane dehalogenases

Štěpánková

Damborský

Chaloupková

2013

Biotechnology Journal

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“…2c and 3). These observations are consistent with earlier reports that sucrose prevented the formation of soluble aggregates and slowed the rate of monomer loss in two different mAbs63,64 and a recombinant human interferon‐γ 65. Increases in the thermal stability of the native state were also associated with an increase in the free energy of unfolding in the presence of different sugars66 and in proportion to sucrose concentration67 in several different proteins.…”

Section: Discussionsupporting

confidence: 92%

Correlating Excipient Effects on Conformational and Storage Stability of an IgG1 Monoclonal Antibody with Local Dynamics as Measured by Hydrogen/Deuterium-Exchange Mass Spectrometry

Manikwar

Majumdar

Hickey

et al. 2013

Journal of Pharmaceutical Sciences

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“…Because the stability of antibody molecules is primarily determined by structural features, identification of aggregation-prone motifs in IgG sequences and molecular modeling are implemented as screening tools in the development of stable products (41,42). Additionally, use of appropriate formulation excipients and process buffers is essential to mitigate aggregation (43,44).…”

Section: Aggregationmentioning

confidence: 99%

Heterogeneity of IgGs: Role of Production, Processing, and Storage on Structure and Function

Barton¹,

Spencer²,

Levitskaya³

et al. 2014

ACS Symposium Series

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Detailed monoclonal antibody (mAb) characterization tools have enabled the discovery of structural variations, including many that compromise functionality or have other undesired properties. Size, charge, glycosylation, and disulfide bonding variants; oxidized amino acid residues; and polypeptide chain truncations, extensions, and cleavage points have been identified. Product quality attributes, including detection techniques, published knowledge about the process origins, and quality impacts of these variants are summarized.

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Opposite Effects of Polyols on Antibody Aggregation: Thermal Versus Mechanical Stresses

Cited by 25 publications

References 42 publications

Organic co‐solvents affect activity, stability and enantioselectivity of haloalkane dehalogenases

Organic co‐solvents affect activity, stability and enantioselectivity of haloalkane dehalogenases

Correlating Excipient Effects on Conformational and Storage Stability of an IgG1 Monoclonal Antibody with Local Dynamics as Measured by Hydrogen/Deuterium-Exchange Mass Spectrometry

Heterogeneity of IgGs: Role of Production, Processing, and Storage on Structure and Function

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