Comparison

Exenatide vs SS-31

Function

While Exenatide is used for type 2 diabetes treatment to improve glycemic control and modestly reduce body weight through GLP-1–like insulinotropic and glucagonostatic effects6768, SS-31 improves mitochondrial bioenergetics, reduces oxidative stress, and shows protective effects in models of ischemia-reperfusion, neurodegeneration, and other mitochondrial disorders4637137.

Mechanism

While Exenatide works as a 39-amino-acid exendin-4 peptide originally isolated from Gila monster venom that acts as a long-acting GLP-1 receptor agonist resistant to DPP-4 degradation67, SS-31 is a mitochondria-targeted tetrapeptide, d-Arg-dimethylTyr-Lys-Phe-NH2, that selectively binds cardiolipin in the inner mitochondrial membrane, stabilizing cristae structure, improving electron transport, and reducing ROS production4637137143.

Length and Sequence

Exenatide is 39 amino acids long, whereas SS-31 is shorter as it has a length of 4 amino acids. Exenatide is made up of a sequence of sequence data not available in the current dataset. SS-31 is made up of a sequence of Arginine, dimethylTyr, Lysine, Phenylalanine.

Receptor

Exenatide

GLP-1 receptor (GLP1R) 6780

SS-31

Cardiolipin-rich inner mitochondrial membrane; interacts with cardiolipin and associated mitochondrial proteins rather than a classical cell-surface receptor46137143

Organism or Origin

Exenatide

Originally from Heloderma suspectum (Gila monster) venom; now produced synthetically67

SS-31

Fully synthetic Szeto–Schiller tetrapeptide; not encoded in the genome4637

Gene

Exenatide

Not assigned in the current dataset.

SS-31

Not assigned in the current dataset.

Sources

67Exendin 4 – Potent GLP-1R agonist - SB PEPTIDE, https://www.sb-peptide.com/project/exendin-4-potent-glp-1r-agonist/
68Glucagon-like peptide-1 analogues: An overview - PMC, https://pmc.ncbi.nlm.nih.gov/articles/PMC3712370/
80GLP-1 Localisation and Proglucagon Gene Expression in ..., https://pmc.ncbi.nlm.nih.gov/articles/PMC6200298/
46Discovery of novel SS-31 (d-Arg-dimethylTyr-Lys-Phe-NH2 ... - PMC, https://pmc.ncbi.nlm.nih.gov/articles/PMC11409442/
56Discovery of novel SS-31 (d-Arg-dimethylTyr-Lys-Phe-NH2 ..., https://pubs.rsc.org/en/content/articlelanding/2024/ra/d4ra05517a
137Mitochondrial protein interaction landscape of SS-31 | PNAS, https://www.pnas.org/doi/10.1073/pnas.2002250117
143SS-31 Peptide: Mitochondrial Repair for Energy and Longevity, https://revolutionhealth.org/blogs/news/peptide-therapy-ss-31