Albumin binding half-life extension: difference between revisions
Diff·revision 14 → 15·10:07, 25 May 2025
Difference between revision 14 and revision 15 of Albumin binding half-life extension. 8 lines changed; the page grew by 1,149 bytes.
| Revision 14 — 15:09, 28 Apr 2025 ReceptorRhoda (talk) split §Physiology from §Pharmacological exploitation 4,872 bytes ±0 | Revision 15 — 10:07, 25 May 2025 AmylinAmos (talk) move the trial material out of §Physiology into the compound articles 6,021 bytes +1,149 | ||
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| 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}} | 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 | 36 | ||
| + | 37 | == Analytical consequences == | |
| + | 38 | Acylated peptides behave differently from their unmodified parents in almost every assay. They are markedly more hydrophobic and retain much longer on [[Reverse-phase HPLC|reverse-phase]] columns, requiring higher organic content and often an elevated column temperature to elute with acceptable peak shape.{{r|usp1503}} | |
| + | 39 | ||
| + | 40 | They also self-associate. Acylated incretin analogues form oligomers in concentrated solution, which is part of what stabilises the marketed formulations but which complicates [[Peptide aggregation|aggregation]] assessment: an apparent high-molecular-weight species may be a reversible oligomer rather than an irreversible aggregate, and size-exclusion chromatography under dissociating and non-dissociating conditions will disagree.{{r|ich_q6b}} | |
| + | 41 | ||
| 37 | == References == | 42 | == References == |
| 38 | {{reflist}} | 43 | {{reflist}} |
| 39 | <ref name="knudsen2019">Knudsen LB, Lau J. "The discovery and development of liraglutide and semaglutide." ''Frontiers in Endocrinology'' 10:155 (2019). PMID 31031702.</ref> | 44 | <ref name="knudsen2019">Knudsen LB, Lau J. "The discovery and development of liraglutide and semaglutide." ''Frontiers in Endocrinology'' 10:155 (2019). PMID 31031702.</ref> |
| 40 | <ref name="lau2015">Lau J, Bloch P, Schäffer L, et al. "Discovery of the once-weekly glucagon-like peptide-1 analog semaglutide." ''Journal of Medicinal Chemistry'' 58(18):7370–7380 (2015). DOI:10.1021/acs.jmedchem.5b00726. PMID 26308095.</ref> | 45 | <ref name="lau2015">Lau J, Bloch P, Schäffer L, et al. "Discovery of the once-weekly glucagon-like peptide-1 analog semaglutide." ''Journal of Medicinal Chemistry'' 58(18):7370–7380 (2015). DOI:10.1021/acs.jmedchem.5b00726. PMID 26308095.</ref> |
| + | 46 | <ref name="usp1503">United States Pharmacopeia, General Chapter <1503>, ''Quality Attributes of Synthetic Peptide Drug Substances''.</ref> | |
| + | 47 | <ref name="ich_q6b">International Council for Harmonisation, ''Q6B: Specifications — Test Procedures and Acceptance Criteria for Biotechnological/Biological Products'' (1999).</ref> | |
| 41 | 48 | ||
| 42 | == See also == | 49 | == See also == |
| ⋮ | ⋮ | ||
| 45 | * [[GLP-1 receptor agonist]] | 52 | * [[GLP-1 receptor agonist]] |
| 46 | * [[Dipeptidyl peptidase-4]] | 53 | * [[Dipeptidyl peptidase-4]] |
| + | 54 | * [[Peptide aggregation]] | |
| 47 | 55 | ||
| 48 | {{DEFAULTSORT:Albumin binding half-life extension}} | 56 | {{DEFAULTSORT:Albumin binding half-life extension}} |