Linked Life Data

18201853

Source:http://linkedlifedata.com/resource/pubmed/id/18201853

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-4-11
pubmed:abstractText
Two degradations of aspartate residues located in Asp-Asp motifs in the CDR3 region of a recombinant monoclonal antibody were identified and quantified after the antibody was aged in a mildly acidic buffer at elevated temperatures. The degraded sample aged at 25 degrees C for 1 month generated 1.8% antibody molecules that had isomerization in the aspartate residues, while the degraded sample after aging at 45 degrees C for 1 month contained 7% isomerization. Peptide bond cleavages at the aspartate residues were also detected and characterized. The percentage of clipped antibody molecules after 1 month of storage was 1% at 25 degrees C and 4.4% at 45 degrees C. The generated cleaved polypeptides were noncovalently attached to the intact antibody molecule and were not involved in the aggregation formation. They were not detected by native size-exclusion chromatography because of their strong non-covalent association to the rest of the antibody molecules. On the other hand, the cleaved polypeptides were dissociated and detected as fragments under denaturing conditions of reversed-phase HPLC, denaturing size-exclusion chromatography and MALDI-TOF mass spectrometry. It was demonstrated that the cleavages at the above aspartate residue sites occurred due to the aging of the sample at elevated temperatures and were not method-induced by the reversed-phase HPLC and other methods used in this study.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0731-7085
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23-30
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Identification and quantification of degradations in the Asp-Asp motifs of a recombinant monoclonal antibody.
pubmed:affiliation
Amgen, Department of Pharmaceutics, One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
pubmed:publicationType
Journal Article