Semaglutide Structure
Semaglutide is a single modified peptide, not multiple peptides—it consists of one continuous peptide chain with 31 amino acids. 1
Molecular Composition
Semaglutide is a GLP-1 analog with 94% sequence homology to human GLP-1, functioning as a single peptide molecule. 1
The molecular formula is C187H291N45O59 with a molecular weight of 4113.58 g/mol, representing one complete peptide structure. 1
The peptide backbone is produced by yeast fermentation and contains specific modifications at three positions to enhance its pharmacological properties. 1
Structural Modifications
Position 8 modification provides stabilization against degradation by dipeptidyl-peptidase 4 (DPP-4) enzyme. 1
Position 26 lysine is modified with a hydrophilic spacer and a C18 fatty di-acid to facilitate albumin binding, which is the main protraction mechanism. 1
Position 34 contains a minor modification to ensure attachment of only one fatty di-acid. 1
Clinical Significance of Single-Peptide Structure
The albumin binding facilitated by the fatty acid modification results in decreased renal clearance and protection from metabolic degradation, enabling once-weekly dosing with a half-life of approximately 7 days. 1, 2
This single-peptide structure with strategic modifications allows semaglutide to reach steady state in 4-5 weeks and maintain therapeutic levels throughout the week. 2