Deamidation: difference between revisions
Diff·revision 6 → 7·06:26, 21 Dec 2024
Difference between revision 6 and revision 7 of Deamidation. 3 lines changed; the page grew by 550 bytes.
| Revision 6 — 15:43, 4 Dec 2024 AnalyticalAnnie (talk) add category for method validation 2,345 bytes +38 | Revision 7 — 06:26, 21 Dec 2024 Areapercent_Ayo (talk) add the cross-link to the compendial chapter 2,895 bytes +550 | ||
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| 18 | Isoaspartate formation is the more damaging outcome, because it inserts an extra methylene into the backbone and changes the local conformation. It is isobaric with aspartate and is not distinguishable by intact mass; detection requires a specific enzymatic or chromatographic method. | 18 | Isoaspartate formation is the more damaging outcome, because it inserts an extra methylene into the backbone and changes the local conformation. It is isobaric with aspartate and is not distinguishable by intact mass; detection requires a specific enzymatic or chromatographic method. |
| 19 | 19 | ||
| + | 20 | Rate rises with pH above about 6, with temperature, and with the flexibility of the local backbone. The Asn-Gly context is the fastest by a wide margin; Asn-Ser and Asn-His are also comparatively fast. Glutamine deamidates by the same mechanism but far more slowly, because the corresponding intermediate is a six-membered ring.{{r|manning2010}} | |
| + | 21 | ||
| 20 | == References == | 22 | == References == |
| 21 | {{reflist}} | 23 | {{reflist}} |
| 22 | <ref name="robinson2001">Robinson NE, Robinson AB. "Molecular clocks." ''Proceedings of the National Academy of Sciences'' 98(3):944–949 (2001). DOI:10.1073/pnas.98.3.944. PMID 11158575.</ref> | 24 | <ref name="robinson2001">Robinson NE, Robinson AB. "Molecular clocks." ''Proceedings of the National Academy of Sciences'' 98(3):944–949 (2001). DOI:10.1073/pnas.98.3.944. PMID 11158575.</ref> |
| + | 25 | <ref name="manning2010">Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. "Stability of protein pharmaceuticals: an update." ''Pharmaceutical Research'' 27(4):544–575 (2010). PMID 20143256.</ref> | |
| 23 | <ref name="usp1503">United States Pharmacopeia, General Chapter <1503>, ''Quality Attributes of Synthetic Peptide Drug Substances''.</ref> | 26 | <ref name="usp1503">United States Pharmacopeia, General Chapter <1503>, ''Quality Attributes of Synthetic Peptide Drug Substances''.</ref> |
| 24 | 27 |