Exenatide is a GLP-1 receptor agonist with a half-life of ~2.4 hours despite GLP-1 itself having a half-life of <2 minutes. The structural modification that confers this resistance to degradation is:
- A Amino acid substitution at position 2 and addition of a fatty acid chain for albumin binding
- B PEGylation of the molecule reducing renal filtration and immune recognition
- C Replacement of the penultimate alanine with glycine at position 2, preventing DPP-4 cleavage ✓
- D Glycosylation protecting the peptide backbone from proteolytic enzymes
Correct answer: C. Replacement of the penultimate alanine with glycine at position 2, preventing DPP-4 cleavage
Explanation
Native GLP-1 is rapidly cleaved by DPP-4 at the Ala-Glu bond between positions 2 and 3. Exenatide (derived from exendin-4, a Gila monster peptide) has a non-alanine residue at position 2 (glycine), making it resistant to DPP-4-mediated cleavage. Liraglutide uses a different strategy — attaching a fatty acid chain to enable albumin binding, extending its half-life to ~13 hours. Semaglutide combines both approaches for a ~7-day half-life.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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