Evidence for a novel racemization process of an asparaginyl residue in mouse lysozyme under physiological conditions

Ueno, K.; Ueda, Tadashi; Sakai, Koyu; Abe, Yoshito; Hamasaki, N; Okamoto, Masahiro; Imoto, Taiji

doi:10.1007/s00018-004-4412-5

Cited by 9 publications

(7 citation statements)

References 103 publications

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“…Typically, the racemization occurs at Asp residues (138), although racemization at Asn 127 in murine lysozyme has been reported (139). Why this residue is more reactive is not yet known.…”

Section: Racemization and β-Eliminationmentioning

confidence: 98%

Stability of Protein Pharmaceuticals: An Update

Manning¹,

Chou²,

Murphy³

et al. 2010

Pharm Res

994

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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“…Typically, the racemization occurs at Asp residues (138), although racemization at Asn 127 in murine lysozyme has been reported (139). Why this residue is more reactive is not yet known.…”

Section: Racemization and β-Eliminationmentioning

confidence: 98%

Stability of Protein Pharmaceuticals: An Update

Manning¹,

Chou²,

Murphy³

et al. 2010

Pharm Res

994

782

View full text Add to dashboard Cite

show abstract

“…Because Asp residues can be easily transformed into succinimidyl intermediates, the chiral inversion from L-Asp to D-Asp frequently occurs, therefore, D-Asp residues are often observed in disease/aged proteins [6]. However, some other D-amino acid residues, such as D-Ser and D-Asn, were also formed in a few protein samples [13][14][15]. These reports suggest that various D-amino acid residues are likely to occur without the formation of succinimidyl intermediates.…”

Section: Introductionmentioning

confidence: 99%

Establishment of a Two-Dimensional HPLC-MS/MS Method Combined with DCl/D<sub>2</sub>O Hydrolysis for the Determination of Trace Amounts of D-Amino Acid Residues in Proteins

Ishigo

Negishi²,

Miyoshi

et al. 2015

Chromatography

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A two-dimensional (2D) HPLC-MS/MS method has been established for the determination of trace amounts of D-amino acid residues in proteins. D-Amino acid residues are now increasingly recognized as biomarkers of diseases and key moieties for the regulation of protein structures/functions, therefore, a sensitive analytical method is highly required. However, non-negligible amounts of D-amino acids are produced by chemical racemization during the hydrolysis of proteins, and a sensitive determination of D-amino acid residues is normally difficult. In the present study, DCl/D 2 O hydrolysis is adopted and the produced deuterated D-amino acids are distinguished from naturally-occurring D-amino acids in the proteins using the 2D-HPLC-MS/MS system. D-Ala, D-Asp, D-Glu, D-Pro and D-Ser (frequently observed D-amino acids in higher animals) were selected as the targets, and the sensitive determination (around 1% or less of the L-forms) could be carried out. As an application, the D-amino acid residues in ovalbumin (OVA) were determined, and the presence of a significant amount of D-Ser (1.8% of L-Ser) was demonstrated.

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“…[85] Other studies have cast doubt on the relevance of cyclic speciesf avouring ah omolysisvia ar adical. [126] Scheme22. Twoc ysteine residues drive racemisation in proline racemase.…”

Section: Racemisation (Or Epimerisation) Of Proteins and Amino Acidsmentioning

confidence: 99%

“…Recent results have suggested that anionic intermediates that have the possibility of aromatic character can enhance racemisation liability and it is noteworthy that the keto–enol tautomer of 55 would fall into this category . Other studies have cast doubt on the relevance of cyclic species favouring a homolysis via a radical …”

Section: Biological Racemisationmentioning

confidence: 99%

Racemisation in Chemistry and Biology

Ballard

Narduolo

Ahmed

et al. 2020

Chemistry A European J

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The two enantiomers of a compound often have profoundly different biological properties and thus their liability to racemisation in aqueous solutions is an important piece of information. The authors reviewed the available data concerning the process of racemisation in vivo, in the presence of biological molecules (e.g., racemase enzymes, serum albumin, cofactors and derivatives) and under purely chemical but aqueous conditions (acid, base and other aqueous systems). Mechanistic studies are described critically in light of reported kinetic data. The types of experimental measurement that can be used to effectively determine rate constants of racemisation in various conditions are discussed and the data they provide is summarised. The proposed origins of enzymatic racemisation are presented and suggest ways to promote the process that are different from processes taking place in bulk water. Experimental and computational studies that provide understanding and quantitative predictions of racemisation risk are also presented.

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Evidence for a novel racemization process of an asparaginyl residue in mouse lysozyme under physiological conditions

Cited by 9 publications

References 103 publications

Stability of Protein Pharmaceuticals: An Update

Stability of Protein Pharmaceuticals: An Update

Establishment of a Two-Dimensional HPLC-MS/MS Method Combined with DCl/D<sub>2</sub>O Hydrolysis for the Determination of Trace Amounts of D-Amino Acid Residues in Proteins

Racemisation in Chemistry and Biology

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