Liraglutide (a GLP-1 receptor agonist) has a much longer half-life than native GLP-1. The structural modification responsible for this is:
- A It is formulated with protamine to delay absorption from injection site
- B Addition of a C-16 fatty acid chain via a glutamate-miniPEG spacer, enabling albumin binding that retards DPP-4 degradation and renal clearance ✓
- C Substitution of alanine at position 2 with glycine, preventing DPP-4 cleavage
- D It is an acylated prodrug that is slowly de-acylated to active form
Correct answer: B. Addition of a C-16 fatty acid chain via a glutamate-miniPEG spacer, enabling albumin binding that retards DPP-4 degradation and renal clearance
Explanation
Liraglutide has a C-16 fatty acid (palmitic acid) attached via a glutamic acid-miniPEG linker, which allows reversible binding to circulating albumin; this albumin-binding sterically hinders DPP-4 access (DPP-4 normally cleaves native GLP-1 within 2 minutes) and reduces renal filtration, extending the half-life to ~13 hours allowing once-daily dosing. Semaglutide uses a similar strategy with a longer C-18 fatty diacid linker, extending half-life to ~7 days.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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