Exenatide: difference between revisions
Diff·revision 3 → 4·08:42, 20 Oct 2024
Difference between revision 3 and revision 4 of Exenatide. 5 lines changed; the page grew by 715 bytes.
| Revision 3 — 10:48, 6 Oct 2024 LiraLotte (talk) ce 1,276 bytes ±0 | Revision 4 — 08:42, 20 Oct 2024 Retention_Time_Rae (talk) state plainly that the research-use-only form is not approved for human use 1,991 bytes +715 | ||
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| 11 | Its therapeutic relevance rests on an accident of sequence: exendin-4 carries glycine rather than alanine at position 2, so [[Dipeptidyl peptidase-4|DPP-4]] does not cleave it. No engineering was required to obtain protease resistance — the peptide is naturally resistant, and this is why a venom peptide became a diabetes drug.{{r|nielsen2004}} | 11 | Its therapeutic relevance rests on an accident of sequence: exendin-4 carries glycine rather than alanine at position 2, so [[Dipeptidyl peptidase-4|DPP-4]] does not cleave it. No engineering was required to obtain protease resistance — the peptide is naturally resistant, and this is why a venom peptide became a diabetes drug.{{r|nielsen2004}} |
| 12 | 12 | ||
| + | 13 | == Origin and sequence == | |
| + | 14 | Exendin-4 was identified in Gila monster venom in the early 1990s and shown to bind the mammalian GLP-1 receptor with high affinity despite substantial sequence divergence. The peptide is not a lizard GLP-1 orthologue; lizards have their own GLP-1, and exendin-4 is a separate gene product expressed in the salivary gland.{{r|nielsen2004}} | |
| + | 15 | ||
| + | 16 | The C-terminal nine residues, absent from human GLP-1, form a tryptophan-cage motif that stabilises the helix and contributes to receptor affinity. This "Trp-cage" extension is the reason exendin-4 binds more tightly than native GLP-1 and is a frequently cited example of a natural product outperforming the endogenous ligand at its own receptor. | |
| + | 17 | ||
| 13 | == References == | 18 | == References == |
| 14 | {{reflist}} | 19 | {{reflist}} |