A Mechanism-Based Kinetic Analysis of Succinimide-Mediated Deamidation, Racemization, and Covalent Adduct Formation in a Model Peptide in Amorphous Lyophiles

DeHart, Michael P.; Anderson, Bradley D.

doi:10.1002/jps.23061

Cited by 5 publications

(1 citation statement)

References 39 publications

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“…3D), whereas the treatment caused the appearance of an additional band at Ͼ250 kDa. These data suggest that the treatment generating reactive succinimide intermediates on Cp may cause intermolecular aggregation, likely caused by reaction with the amino group present in neighbor Cp molecules (29). Remarkably, both products, full-length Cp and aggregates, bind ␣v␤6 integrin (Fig.…”

Section: Accelerated Aging Of Cp Under Oxidative Conditions Causesmentioning

confidence: 85%

Oxidation-induced Structural Changes of Ceruloplasmin Foster NGR Motif Deamidation That Promotes Integrin Binding and Signaling

Barbariga

Curnis

Spitaleri

et al. 2014

Journal of Biological Chemistry

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Background: Asparagine deamidation at Asn-Gly-Arg (NGR) sites leads to the isoAsp-Gly-Arg (isoDGR) integrin-binding motif formation. Results: Ceruloplasmin (Cp), which contains two NGR sites and is oxidized in cerebrospinal fluid (CSF) in neurodegenerative diseases, can, undergo oxidation-induced structural changes fostering NGR deamidation with gain of integrin binding and signaling properties, in vitro and ex vivo in pathological CSF. Conclusion: Cp NGR motifs can deamidate acquiring integrin-binding functions. Significance: Cp structural changes favor NGR deamidation.

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Section: Accelerated Aging Of Cp Under Oxidative Conditions Causesmentioning

confidence: 85%

Oxidation-induced Structural Changes of Ceruloplasmin Foster NGR Motif Deamidation That Promotes Integrin Binding and Signaling

Barbariga

Curnis

Spitaleri

et al. 2014

Journal of Biological Chemistry

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Process Development of Protein Therapeutics

Huang¹,

Bowes²,

Yang³

et al. 2021

Burger's Medicinal Chemistry and Drug Discovery

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The application of recombinant DNA technology to the production of protein therapeutics has undergone tremendous progress over the past decades. Considerable scientific effort has been devoted to developing robust processes that produce large amounts of complex proteins with the desired product quality attributes. An overview of the contributions from the four major disciplines working in concert to deliver these processes and methods will be covered. This article will discuss some of the tools, methods, and approaches used to produce, purify, formulate, and analyze the drugs of modern biotechnology. Future trends in each of the disciplines will also be presented.

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Molecular Dynamics Simulations of Amorphous Systems

Anderson

Xiang

2016

Computational Pharmaceutical Solid State Chemistry

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A Mechanism-Based Kinetic Analysis of Succinimide-Mediated Deamidation, Racemization, and Covalent Adduct Formation in a Model Peptide in Amorphous Lyophiles

Cited by 5 publications

References 39 publications

Oxidation-induced Structural Changes of Ceruloplasmin Foster NGR Motif Deamidation That Promotes Integrin Binding and Signaling

Oxidation-induced Structural Changes of Ceruloplasmin Foster NGR Motif Deamidation That Promotes Integrin Binding and Signaling

Process Development of Protein Therapeutics

Molecular Dynamics Simulations of Amorphous Systems

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