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- W3120405663 abstract "Aspartic acid (Asp) to isoaspartic acid (isoAsp) isomerization in therapeutic monoclonal antibodies (mAbs) and other biotherapeutics is a critical quality attribute (CQA) that requires careful control and monitoring during the drug discovery and production processes. The unwanted formation of isoAsp within biotherapeutics and resultant structural changes in the peptide backbone may negatively impact the efficacy, potency, and safety of the molecule or become immunogenic, especially if the isomerization occurs within the mAb complementarity determining region (CDR). Herein we describe a MALDI-TOF/TOF mass spectrometry method that affords unequivocal identification of the presence and the exact position of the isoAsp residue(s) in peptide standards ranging in size from a tripeptide to a docosapeptide (22 residues). In general, the peptide bond immediately N-terminal to the isoAsp residue is more susceptible to MALDI-TOF/TOF fragmentation than its unmodified counterpart. In some of the peptides evaluated in this study, fragmentation of the peptide bond C-terminal to the isoAsp residue (the aspartate effect) is also enhanced when compared to the control. Relative quantification by MALDI-TOF/TOF of this chemical modification is dependent upon a successful reversed-phase HPLC (rpHPLC) separation of the control and modified peptides. This method has also been validated on a therapeutic mAb that contains a well-documented isoAsp residue in the heavy chain CDR3 after forced degradation. Moreover, we also demonstrate that higher energy C-trap dissociation of only the singly charged species, and not the multiply charged form, of the isoAsp containing peptide, separated by rpHPLC, results in LC-MS/MS fragmentation that is highly consistent to that of MALDI-TOF/TOF." @default.
- W3120405663 created "2021-01-18" @default.
- W3120405663 creator A5003299197 @default.
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- W3120405663 creator A5034846248 @default.
- W3120405663 date "2021-01-04" @default.
- W3120405663 modified "2023-10-09" @default.
- W3120405663 title "Unequivocal Identification of Aspartic Acid and <i>iso</i>Aspartic Acid by MALDI-TOF/TOF: From Peptide Standards to a Therapeutic Antibody" @default.
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- W3120405663 doi "https://doi.org/10.1021/jasms.0c00370" @default.
- W3120405663 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33390012" @default.
- W3120405663 hasPublicationYear "2021" @default.
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