(Ser8)-GLP-1 (7-36), amide, human

[Ser8]-GLP-1 (7-36) Amide (Human) is a single-residue substituted analog of the endogenous incretin peptide GLP-1 (7-36) amide in which the Ala8 (position 8, counting from the full proglucagon-derived N-terminus) has been replaced with serine. This substitution was designed to confer resistance to dipeptidyl peptidase IV (DPP-IV/CD26), the serine protease that cleaves the native peptide at the His7-Ala8 bond, rapidly inactivating intact GLP-1 (7-36) in plasma. By replacing the penultimate N-terminal alanine with serine, [Ser8]-GLP-1 retains the core 28-residue helix-forming backbone required for glucagon-like peptide receptor (GLP-1R) binding while substantially slowing DPP-IV recognition in in vitro degradation assays.

Potential Research Applications: DPP-IV stability and metabolic half-life studies — comparing degradation kinetics of [Ser8]-GLP-1 vs. native GLP-1 (7-36) in plasma or membrane-fraction assays Structure-activity relationship (SAR) studies at position 8 of GLP-1 analogs, complementing studies with [Aib8]- and other Ala8-modified variants GLP-1 receptor binding and cAMP signaling studies in cell lines expressing human GLP-1R (InR, HEK293-GLP1R, INS-1), as the [Ser8] substitution is generally considered GLP-1R-agonistic at the receptor level despite improved metabolic stability Comparative control for native GLP-1 (7-36) in time-course degradation experiments

What the Founding Study Reported

The Ser8 analog comes from a 1998 Diabetologia study that synthesized four N-terminally substituted GLP-1 analogs (threonine, glycine, serine, or α-aminoisobutyric acid at position 8) and tested their metabolic stability. All four were more resistant to dipeptidyl peptidase IV in porcine plasma than native GLP-1 (7-36) amide (t1/2 28 min), ranging from 159 min for the Gly8 analog to no detectable degradation after 6 h for the Aib8 analog. During intravenous infusion in anesthetized pigs, more than 50% of each analog remained intact compared with 22.7% of native GLP-1, and intact-peptide half-lives were longer (3.3–3.9 min versus 0.9 min). Receptor binding and insulin-stimulating activity at the isolated perfused porcine pancreas were retained, though only the Aib8 and Gly8 analogs matched native affinity. That ranking (Aib8 most stable, Ser8 intermediate) is the reason the Ser8 analog is a useful intermediate-stability comparator rather than a lead compound, and it is the same Aib8 substitution that was later built into semaglutide.

The degradation problem the analog was designed to address is anatomically specific. A 1999 Endocrinology study showed that GLP-1 (7-36) amide is converted to the inactive (9-36) form by DPP-IV located in the capillary endothelium adjacent to intestinal L cells, so that only 33% of newly secreted GLP-1 reached the portal circulation intact in vivo, rising to near 100% with a DPP-IV inhibitor. The Ser8 substitution has also been carried into recombinant constructs: a 2007 Biotechnology Letters study expressed a fusion protein of eight tandem [Ser8, Gln26, Asp34]-GLP-1 repeats in E. coli for oral administration studies in streptozotocin-diabetic rats.

Live Market Data on Peptides.SO (listing data on file as of 13 September 2026)

Peptides.SO currently tracks 1 listing for [Ser8]-GLP-1 (7-36) amide (human), from CPC Scientific at $104.50 (priced per mg on the listing). The median list price across the 731 priced listings in the platform's GLP-1 agonist category is $129.00, so this analog sits about 19% below the category midpoint. That is unusual for a custom analog; the category median is set by semaglutide and tirzepatide vials sold in larger masses. For the native peptide and the approved analogs, see the semaglutide and liraglutide pages, which aggregate 51 and multiple supplier listings respectively. No supplier on the platform currently has a testing score or certificate-of-analysis link on file; confirm the position-8 serine by mass spectrometry, since Ala8 native GLP-1 differs by only 16 Da.

Frequently Asked Questions

How does Ser8 compare to Aib8 (the semaglutide substitution)? In the founding study Aib8 conferred complete DPP-IV resistance over 6 h and retained native receptor affinity; Ser8 conferred partial resistance with somewhat reduced affinity. Ser8 is therefore the better tool for studying intermediate stability, not maximal stability.

Is this analog a GLP-1 receptor agonist? Yes at the receptor level; it retained binding and insulin-stimulating activity at the perfused porcine pancreas, though with lower affinity than the Aib8 and Gly8 analogs.

What is the difference between (7-36) amide and (7-37)? Both are biologically active forms of GLP-1; (7-36) amide is the predominant circulating form in humans. The numbering counts from the proglucagon-derived N-terminus, so position 8 is the second residue of the mature peptide.

Related Pages on Peptides.SO

Background reading: the GLP-1 receptor agonist research overview, the GLP-1 peptide half-life guide, and the GLP-1 receptor agonist mechanism comparison. Use the reconstitution calculator for molar stock preparation.

Cited Research

Deacon CF et al.. Dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1 which have extended metabolic stability and improved biological activity. Diabetologia. 1998. PubMed 9541166

Hansen L et al.. Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9-36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine. Endocrinology. 1999. PubMed 10537167

Hou J et al.. Oral administration of a fusion protein containing eight GLP-1 analogues produced in Escherichia coli BL21(DE3) in streptozotocin-induced diabetic rats. Biotechnol Lett. 2007. PubMed 17581704

For laboratory research use only. Not for human or veterinary use, diagnosis, treatment, cure, or prevention of any disease. THIS PRODUCT IS NOT FOR HUMAN CONSUMPTION.