Semaglutide: Difference between revisions

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Semaglutide was discovered <ref name = "discovery">PMID:26308095</ref> in an effort to increase the lifetime of a once-a-day medication called Liraglutide. It is derived from the [[GLP-1]] hormone, contains two amino acid sequence changes and a covalently attached lipid.

==Structure and binding to GLP-1R==<StructureSection load='' size='340' side='right' caption='' scene='10/1062575/Semaglutide_and_receptor/2'>

~~==Structure and binding to GLP-1R==~~

The primary structure of GLP-1 and of semaglutide are shown below. Semaglutide has a non-canonical amino acid in position 8 (corresponding to the second amino acid in the mature 7-37 peptide hormone). A fatty acid is attached is attached to the single lysine in semaglutide via a linker.

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[[Image:GLP1 DPP4 processing.png|600px]]

Synthetic agonists like semaglutide are engineered to resist degradation by DPP-4. The drug developers substituted ~~Alanine-~~8 with aminoisobutyric acid (Alb) and added a stabilizing fatty acid chain at lysine-26. These modifications alter the recognition sequence for the DPP-4’s active site and the fatty acid chain allows the protein to bind to albumin, which prolongs the drugs’ stability in the bloodstream. DPP-4 inhibitors are useful to decrease the enzyme’s total activity (resulting in a higher GLP-1 concentration), and are administered on their own or in combination with synthetic agonists. The inhibitors come in multiple forms, all in the gliptin class, and these competitively inhibit DPP-4 by binding to its active site instead of GLP-1 or analogs.

Synthetic agonists like semaglutide are engineered to resist degradation by DPP-4. The drug developers substituted alanine 8 with aminoisobutyric acid (Alb) and added a stabilizing fatty acid chain at lysine-26. These modifications alter the recognition sequence for the DPP-4’s active site and the fatty acid chain allows the protein to bind to albumin, which prolongs the drugs’ stability in the bloodstream. DPP-4 inhibitors are useful to decrease the enzyme’s total activity (resulting in a higher GLP-1 concentration), and are administered on their own or in combination with synthetic agonists. The inhibitors come in multiple forms, all in the gliptin class, and these competitively inhibit DPP-4 by binding to its active site instead of GLP-1 or analogs.

</StructureSection>

Semaglutide: Difference between revisions

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@@ Line 7: / Line 7: @@
 Semaglutide was discovered <ref name = "discovery">PMID:26308095</ref> in an effort to increase the lifetime of a once-a-day medication called Liraglutide. It is derived from the [[GLP-1]] hormone, contains two amino acid sequence changes and a covalently attached lipid.
-<StructureSection load='' size='340' side='right' caption='' scene='10/1062575/Semaglutide_and_receptor/2'>
+==Structure and binding to GLP-1R==<StructureSection load='' size='340' side='right' caption='' scene='10/1062575/Semaglutide_and_receptor/2'>
-==Structure and binding to GLP-1R==
 The primary structure of GLP-1 and of semaglutide are shown below. Semaglutide has a non-canonical amino acid in position 8 (corresponding to the second amino acid in the mature 7-37 peptide hormone). A fatty acid is attached is attached to the single lysine in semaglutide via a linker.
@@ Line 147: / Line 146: @@
 [[Image:GLP1 DPP4 processing.png|600px]]
-Synthetic agonists like semaglutide are engineered to resist degradation by DPP-4. The drug developers substituted Alanine-8 with aminoisobutyric acid (Alb) and added a stabilizing fatty acid chain at lysine-26. These modifications alter the recognition sequence for the DPP-4’s active site and the fatty acid chain allows the protein to bind to albumin, which prolongs the drugs’ stability in the bloodstream. DPP-4 inhibitors are useful to decrease the enzyme’s total activity (resulting in a higher GLP-1 concentration), and are administered on their own or in combination with synthetic agonists. The inhibitors come in multiple forms, all in the gliptin class, and these competitively inhibit DPP-4 by binding to its active site instead of GLP-1 or analogs.
+Synthetic agonists like semaglutide are engineered to resist degradation by DPP-4. The drug developers substituted alanine 8 with aminoisobutyric acid (Alb) and added a stabilizing fatty acid chain at lysine-26. These modifications alter the recognition sequence for the DPP-4’s active site and the fatty acid chain allows the protein to bind to albumin, which prolongs the drugs’ stability in the bloodstream. DPP-4 inhibitors are useful to decrease the enzyme’s total activity (resulting in a higher GLP-1 concentration), and are administered on their own or in combination with synthetic agonists. The inhibitors come in multiple forms, all in the gliptin class, and these competitively inhibit DPP-4 by binding to its active site instead of GLP-1 or analogs.
 </StructureSection>