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Research Library
Published research on this compound — for educational purposes only
How does GLP-1 S’s acylation enable extended half-life? (for educational purposes only)
GLP-1 S incorporates a C-18 fatty di-acid chain (octadecanedioic acid) attached to lysine at position 26 via a mini-PEG linker (γGlu-2×OEG spacer). This acyl moiety binds non-covalently to serum albumin with high affinity, creating a circulating depot that shields the peptide from renal clearance and enzymatic degradation. The resulting pharmacokinetic half-life of approximately 165 hours (~7 days) enables extended duration. The spacer length and fatty acid chain were specifically optimized to balance albumin binding strength with receptor accessibility. Research compound — not for human use.
Citation: Lau J, Bloch P, Schäffer L, et al. “Discovery of the Long-Acting Glucagon-Like Peptide-1 (GLP-1) Analogue GLP-1 S.” J Med Chem. 2015;58(18):7370-7380. PubMed
How does GLP-1 S’s structure compare to native GLP-1(7-37)? (for educational purposes only)
GLP-1 S shares 94% amino acid sequence homology with endogenous human GLP-1(7-37), differing at only two positions. An α-aminoisobutyric acid (Aib) substitution at position 8 confers resistance to dipeptidyl peptidase-4 (DPP-4) cleavage, which normally inactivates native GLP-1 within 2-3 minutes. Arginine replaces lysine at position 34 to prevent unwanted fatty acid conjugation at that site, directing acylation exclusively to Lys26. These minimal modifications preserve full GLP-1 receptor binding potency while dramatically extending the molecule’s circulating persistence. Research compound — not for human use.
Citation: Lau J, Bloch P, Schäffer L, et al. “Discovery of the Long-Acting Glucagon-Like Peptide-1 (GLP-1) Analogue GLP-1 S.” J Med Chem. 2015;58(18):7370-7380. PubMed
What is GLP-1 S’s GLP-1 receptor binding selectivity? (for educational purposes only)
GLP-1 S is a selective GLP-1 receptor agonist with no meaningful affinity for the GIP receptor, glucagon receptor, or other class B GPCRs. In radioligand binding assays, GLP-1 S displaces GLP-1 from its receptor with an IC₅₀ comparable to native GLP-1, demonstrating preserved binding potency despite structural modifications. The Aib8 substitution and C-18 fatty di-acid acylation do not substantially alter receptor binding affinity or cAMP generation efficacy at GLP-1R. This selectivity profile distinguishes GLP-1 S from multi-receptor agonists such as GLP-2 T. Research compound — not for human use.
Citation: Lau J, Bloch P, Schäffer L, et al. “Discovery of the Long-Acting Glucagon-Like Peptide-1 (GLP-1) Analogue GLP-1 S.” J Med Chem. 2015;58(18):7370-7380. PubMed
How was GLP-1 S’s structure optimized during discovery? (for educational purposes only)
GLP-1 S’s design followed systematic structure-activity relationship studies starting from liraglutide (C-16 acyl chain, once-daily). Researchers evaluated fatty acid chain lengths (C-16 to C-20), spacer compositions (γGlu, OEG combinations), and acylation positions to optimize the balance between albumin binding affinity, GLP-1R potency, and pharmacokinetic half-life. The C-18 di-acid with γGlu-2×OEG spacer at Lys26 yielded the optimal profile: 3-fold stronger albumin affinity than liraglutide while maintaining equivalent receptor activation potency. Over 50 analogs were synthesized and characterized during this optimization process. Research compound — not for human use.
Citation: Lau J, Bloch P, Schäffer L, et al. “Discovery of the Long-Acting Glucagon-Like Peptide-1 (GLP-1) Analogue GLP-1 S.” J Med Chem. 2015;58(18):7370-7380. PubMed
Disclaimer: All research citations are provided for educational purposes only. These references describe findings from in vitro and animal model studies. This information does not constitute medical advice and should not be interpreted as endorsement of any specific application.