Compound Profile: Semaglutide

Semaglutide is a synthetic analogue of human GLP-1(7-37), a 31-amino-acid peptide. Its molecular formula is C187H291N45O59 and its average molecular weight is approximately 4,113.6 g/mol. Relative to native GLP-1 it has two amino-acid substitutions: Aib (2-aminoisobutyric acid) at position 8, which blocks cleavage by dipeptidyl peptidase-4, and arginine at position 34, which removes a lysine so that the fatty-acid chain can be attached site-specifically at the remaining lysine 26.

At lysine 26 the peptide carries a C18 fatty diacid (octadecanedioic acid) attached through a linker of γ-glutamic acid and two 8-amino-3,6-dioxaoctanoic acid units. This chain binds reversibly to serum albumin, protecting the peptide from renal clearance and extending its half-life in published pharmacokinetic work to approximately one week. The approach was developed from liraglutide, an earlier analogue with a C16 monoacid, and was subsequently applied to tirzepatide and retatrutide.

Semaglutide is a full agonist at the GLP-1 receptor with affinity comparable to native GLP-1. It has no activity at the GIP or glucagon receptors, which is what makes it the baseline for the dual- and triple-agonist comparisons that dominate recent incretin literature. GLP-1 receptor activation in published work stimulates glucose-dependent insulin secretion in islet models and acts at receptors in the central nervous system and gastrointestinal tract.

The literature is very large and includes receptor-signalling studies in cell lines, islet and glucose-homeostasis models, energy-balance and adiposity models in rodents, and an extensive clinical programme. In the research-peptide context the compound is used in receptor pharmacology, as a comparator for newer agonists, and in combination studies with amylin analogues such as cagrilintide.

Semaglutide is analysed by reversed-phase HPLC, where the lipidated chain extends retention, and by mass spectrometry against the theoretical mass of the full modified structure. Regent Peptides supplies semaglutide in two vial strengths, UK manufactured, with each batch independently tested by Janoshik Analytical.

Semaglutide is an approved prescription medicine in many jurisdictions under several brand names. The research-grade peptide supplied here is not that product, is not a medicine, and is supplied solely for in-vitro laboratory research. It is not for human use.