Albumin binding half-life extension: difference between revisions
Diff·revision 4 → 5·15:17, 16 Oct 2024
Difference between revision 4 and revision 5 of Albumin binding half-life extension. 3 lines changed; the page grew by 336 bytes.
| Revision 4 — 10:07, 5 Oct 2024 ArchiveBot (talk) bot: sort category members 2,821 bytes +396 | Revision 5 — 15:17, 16 Oct 2024 AmylinAmos (talk) attribute the gastric-emptying effect to the study that measured it 3,157 bytes +336 | ||
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| 10 | The strategy is the basis of the long dosing intervals achieved by [[Liraglutide|liraglutide]] and [[Semaglutide|semaglutide]], and it is used in insulin analogues and in several unrelated peptide drugs. Its principal advantage over covalent fusion to a large carrier is reversibility: the free and bound pools remain in equilibrium, so the peptide retains full receptor activity when released, and the peak-to-trough ratio flattens without the pharmacophore being encumbered.{{r|lau2015}} | 10 | The strategy is the basis of the long dosing intervals achieved by [[Liraglutide|liraglutide]] and [[Semaglutide|semaglutide]], and it is used in insulin analogues and in several unrelated peptide drugs. Its principal advantage over covalent fusion to a large carrier is reversibility: the free and bound pools remain in equilibrium, so the peptide retains full receptor activity when released, and the peak-to-trough ratio flattens without the pharmacophore being encumbered.{{r|lau2015}} |
| 11 | 11 | ||
| + | 12 | Design involves three choices — where to attach, what spacer to use, and which fatty acid. All three are constrained by the requirement that the modification lie distal to the receptor-binding region of the peptide, which for the incretin analogues means the C-terminal half.{{r|knudsen2019}} | |
| + | 13 | ||
| 12 | == Physical basis == | 14 | == Physical basis == |
| 13 | Human serum albumin circulates at roughly 600 μM and carries several hydrophobic binding sites, principally the Sudlow sites, which in physiology transport long-chain fatty acids, bilirubin and a wide range of drugs. A peptide bearing a fatty-acid tail occupies one of these sites with an affinity that can be tuned across several orders of magnitude by chain length and by the presence of a terminal carboxylate.{{r|lau2015}} | 15 | Human serum albumin circulates at roughly 600 μM and carries several hydrophobic binding sites, principally the Sudlow sites, which in physiology transport long-chain fatty acids, bilirubin and a wide range of drugs. A peptide bearing a fatty-acid tail occupies one of these sites with an affinity that can be tuned across several orders of magnitude by chain length and by the presence of a terminal carboxylate.{{r|lau2015}} |
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| 25 | [[Category:Pharmacokinetics]] | 27 | [[Category:Pharmacokinetics]] |
| 26 | [[Category:Peptide synthesis]] | 28 | [[Category:Peptide synthesis]] |
| + | 29 | [[Category:Compounds and pharmacology]] | |
| 27 | 30 |