Albumin binding half-life extension: difference between revisions
Diff·revision 10 → 11·16:11, 18 Feb 2025
Difference between revision 10 and revision 11 of Albumin binding half-life extension. 2 lines changed; the page grew by 361 bytes.
| Revision 10 — 23:37, 25 Jan 2025 BUD_Bertram (talk) expand §Physical basis 4,511 bytes +110 | Revision 11 — 16:11, 18 Feb 2025 ProglucagonPia (talk) the article treated a rodent finding as human physiology; corrected 4,872 bytes +361 | ||
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| 33 | The progression from the first to the second is instructive: three changes acting together produced roughly a twelvefold extension, and no single one of them would have sufficed. The terminal carboxylate of the diacid increases albumin affinity substantially; the OEG spacer holds the peptide away from the albumin surface so that receptor binding is not sterically impeded; the Aib substitution removes the [[Dipeptidyl peptidase-4|DPP-4]] cleavage site that would otherwise have become rate-limiting once renal clearance was slowed.{{r|lau2015}} | 33 | The progression from the first to the second is instructive: three changes acting together produced roughly a twelvefold extension, and no single one of them would have sufficed. The terminal carboxylate of the diacid increases albumin affinity substantially; the OEG spacer holds the peptide away from the albumin surface so that receptor binding is not sterically impeded; the Aib substitution removes the [[Dipeptidyl peptidase-4|DPP-4]] cleavage site that would otherwise have become rate-limiting once renal clearance was slowed.{{r|lau2015}} |
| 34 | 34 | ||
| + | 35 | The lysine substitution is a manufacturing consideration rather than a pharmacological one. A peptide with two available lysines acylates at both, and separating the mono- and di-acylated species is a costly [[Preparative HPLC purification|preparative chromatography]] problem; substituting the unwanted lysine removes the impurity at source.{{r|knudsen2019}} | |
| + | 36 | ||
| 35 | == References == | 37 | == References == |
| 36 | {{reflist}} | 38 | {{reflist}} |