Hormonal
Peptide 20, a GIPR/GLP-1R/GCGR tri-agonist, achieves balanced potency across all three receptors through specific structural modifications, including lipidation of K10P, which stabilizes binding and enhances receptor-mediated cAMP accumulation.
Peptide 20 is a complex drug that activates three metabolic receptors (GIP, GLP-1, Glucagon) simultaneously. Its effectiveness relies on specific chemical modifications (lipidation) that stabilize the drug's binding to these receptors, leading to significant improvements in blood sugar, weight, and glucose tolerance in animal models.
Peptide 20, a GIPR/GLP-1R/GCGR triagonist... with balanced potency at the three receptors... The lipidated K10P greatly stabilized the peptide binding through extensive contacts with both receptors and lipid membrane.
Why this rating
Supported by high-resolution (3.0-3.5 Å) cryo-EM structures and functional assays (cAMP accumulation, binding affinity).
Source
Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors
Fenghui Zhao et al. · Nature Communications · 2022
DOI 10.1038/s41467-022-28683-0
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