Dipeptidyl peptidase-4: difference between revisions
Diff·revision 9 → 10·15:31, 26 Oct 2024
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| 1 | {{Infobox concept | 1 | {{Infobox concept |
| 2 | | name = Dipeptidyl peptidase-4 | 2 | | name = Dipeptidyl peptidase-4 |
| + | 3 | | subtitle = Serine exopeptidase | |
| 3 | | Abbreviation = DPP-4 | 4 | | Abbreviation = DPP-4 |
| 4 | | Also known as = CD26, adenosine deaminase-binding protein | 5 | | Also known as = CD26, adenosine deaminase-binding protein |
| ⋮ | ⋮ | ||
| 9 | | Forms = Membrane-anchored and soluble plasma form | 10 | | Forms = Membrane-anchored and soluble plasma form |
| 10 | }} | 11 | }} |
| + | 12 | {{hatnote|For the hormones this enzyme inactivates, see [[Glucagon-like peptide-1]] and [[Glucose-dependent insulinotropic polypeptide]].}} | |
| 11 | 13 | ||
| 12 | '''Dipeptidyl peptidase-4''' ('''DPP-4'''), also known as '''CD26''', is a serine exopeptidase that removes the N-terminal two residues from peptides presenting proline or alanine in the second position. Both incretin hormones — [[Glucagon-like peptide-1]] and [[Glucose-dependent insulinotropic polypeptide]] — carry alanine at position 2 and are therefore inactivated within minutes of secretion.{{r|deacon2019}} | 14 | '''Dipeptidyl peptidase-4''' ('''DPP-4'''), also known as '''CD26''', is a serine exopeptidase that removes the N-terminal two residues from peptides presenting proline or alanine in the second position. Both incretin hormones — [[Glucagon-like peptide-1]] and [[Glucose-dependent insulinotropic polypeptide]] — carry alanine at position 2 and are therefore inactivated within minutes of secretion.{{r|deacon2019}} |
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| 22 | 24 | ||
| 23 | Kinetically the enzyme is efficient rather than abundant: plasma DPP-4 activity is sufficient to halve circulating intact GLP-1 in about one minute, which is why the intact fraction must be measured with an assay that distinguishes GLP-1(7–36) from GLP-1(9–36) if the measurement is to mean anything. | 25 | Kinetically the enzyme is efficient rather than abundant: plasma DPP-4 activity is sufficient to halve circulating intact GLP-1 in about one minute, which is why the intact fraction must be measured with an assay that distinguishes GLP-1(7–36) from GLP-1(9–36) if the measurement is to mean anything. |
| + | 26 | ||
| + | 27 | == Evading the enzyme == | |
| + | 28 | Every therapeutic peptide agonist in this class solves the DPP-4 problem, and the solutions are few. | |
| + | 29 | ||
| + | 30 | | Approach | Molecule | Modification | | |
| + | 31 | |---|---|---| | |
| + | 32 | | Non-natural residue at position 2 | [[Semaglutide]] | α-aminoisobutyric acid (Aib) at position 8 | | |
| + | 33 | | Naturally resistant scaffold | [[Exenatide]] | Glycine at position 2 of exendin-4 | | |
| + | 34 | | Steric protection by acylation | [[Liraglutide]] | C-16 diacid, albumin-bound fraction shielded | | |
| + | 35 | | Fusion partner | [[Dulaglutide]] | Fc domain, plus Gly substitution | | |
| 24 | 36 | ||
| 25 | == References == | 37 | == References == |