Semaglutide: difference between revisions
Diff·revision 4 → 5·16:04, 7 Jul 2024
Difference between revision 4 and revision 5 of Semaglutide. 3 lines changed; the page grew by 571 bytes.
| Revision 4 — 08:15, 29 Jun 2024 SemaglutideSasha (talk) add see also to the amylin analogue 2,607 bytes +30 | Revision 5 — 16:04, 7 Jul 2024 ComparisonCato (talk) close an unbalanced quotation mark 3,178 bytes +571 | ||
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| 16 | Lys34 was substituted with arginine so that Lys26 is the only lysine available for acylation, which removes a difficult di-acylated impurity from the synthesis rather than requiring it to be separated by [[Preparative HPLC purification|preparative chromatography]]. The acyl group itself is octadecanedioic acid — a C-18 ''diacid'' rather than the C-16 monoacid used in [[Liraglutide|liraglutide]] — attached through a γ-glutamate and two oligoethylene glycol units. | 16 | Lys34 was substituted with arginine so that Lys26 is the only lysine available for acylation, which removes a difficult di-acylated impurity from the synthesis rather than requiring it to be separated by [[Preparative HPLC purification|preparative chromatography]]. The acyl group itself is octadecanedioic acid — a C-18 ''diacid'' rather than the C-16 monoacid used in [[Liraglutide|liraglutide]] — attached through a γ-glutamate and two oligoethylene glycol units. |
| 17 | 17 | ||
| + | 18 | The spacer does real work. It holds the peptide far enough from the albumin surface that the receptor-binding N-terminus remains accessible while the fatty acid is buried in the albumin binding site, so the albumin-bound fraction is a genuine reservoir rather than a sequestered pool. The terminal carboxylate of the diacid raises albumin affinity substantially over a monoacid.{{r|knudsen2019}} | |
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| 18 | == References == | 20 | == References == |
| 19 | {{reflist}} | 21 | {{reflist}} |
| 20 | <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> | 22 | <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> |
| + | 23 | <ref name="knudsen2019">Knudsen LB, Lau J. "The discovery and development of liraglutide and semaglutide." ''Frontiers in Endocrinology'' 10:155 (2019). PMID 31031702.</ref> | |
| 21 | <ref name="lincoff2023">Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. "Semaglutide and cardiovascular outcomes in obesity without diabetes." ''New England Journal of Medicine'' 389(24):2221–2232 (2023). PMID 37952131.</ref> | 24 | <ref name="lincoff2023">Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. "Semaglutide and cardiovascular outcomes in obesity without diabetes." ''New England Journal of Medicine'' 389(24):2221–2232 (2023). PMID 37952131.</ref> |
| 22 | 25 |