Technical Specifications: Retatrutide is a synthetic peptide and a multi-receptor agonist designed to target three specific receptors involved in metabolic regulation: GLP-1 (glucagon-like peptide-1), GIP (gastric inhibitory polypeptide), and glucagon receptors. Its molecular formula is C215H347N61O65 and it has a molecular weight of approximately 4680 Da. Retatrutide is designed to mimic endogenous incretin hormones and other peptides, potentially influencing glucose metabolism, appetite regulation, and energy expenditure through its multi-receptor activity.
Manufacturing Process Information: The synthesis of retatrutide involves solid-phase peptide synthesis (SPPS), a common method used for the production of peptides. This process includes the sequential addition of amino acid residues to a growing peptide chain anchored to a solid resin. The steps typically involve:
- Resin Loading: The initial amino acid is attached to a resin, which acts as the solid support for the synthesis.
- Chain Elongation: Subsequent amino acids are added one at a time in a specific sequence. Each cycle of addition includes deprotection of the terminal amino group, coupling of the next amino acid, and washing steps.
- Cleavage and Deprotection: Once the peptide chain is fully assembled, it is cleaved from the resin and any protecting groups on the amino acid side chains are removed.
- Purification: The crude peptide is purified using techniques such as high-performance liquid chromatography (HPLC) to achieve the desired purity and composition.
- Characterization: The purified peptide is characterized using analytical methods such as mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy to confirm its structure and purity.
Animal Research Information: Retatrutide has undergone extensive preclinical studies in various animal models to evaluate its pharmacological effects, safety profile, and mechanism of action. In rodent studies, retatrutide has demonstrated the ability to influence key metabolic parameters, including:
- Glucose Regulation: Improvements in glucose tolerance and reductions in fasting blood glucose levels.
- Weight Management: Reduction in body weight and adiposity, likely due to decreased food intake and enhanced energy expenditure.
- Lipid Metabolism: Favorable effects on lipid profiles, such as reductions in circulating triglycerides and cholesterol levels.
Studies in non-human primates have provided further insights into the pharmacokinetics, biodistribution, and multi-receptor agonist activity of retatrutide. These studies often involve detailed measurements of the compound's half-life, receptor binding affinities, and downstream signaling pathways.
Animal toxicology studies are also conducted to assess the safety and tolerability of retatrutide, examining potential adverse effects at various dose levels and durations of administration. These studies help establish the safety margins and identify any species-specific responses that may inform further development.
Overall, the comprehensive animal research on retatrutide supports its pharmacological potential and provides a foundational understanding of its multi-faceted mechanisms of action in metabolic regulation.
Here are some references that provide detailed information about the technical specifications, manufacturing processes, and animal research on retatrutide:
- Technical Specifications and Manufacturing Process:
- Merrifield, R. B. (1963). "Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide". Journal of the American Chemical Society. 85 (14): 2149–2154. doi:10.1021/ja00897a025.
- Chan, W. C., & White, P. D. (2000). "Fmoc Solid Phase Peptide Synthesis: A Practical Approach". Oxford University Press. ISBN 978-0199637249.
- Dawson, P. E., Muir, T. W., Clark-Lewis, I., & Kent, S. B. H. (1994). "Synthesis of proteins by native chemical ligation". Science. 266 (5186): 776–779. doi:10.1126/science.7973629.
- Animal Research Information:
- Finan, B., Ma, T., Ottaway, N., Müller, T. D., Habegger, K. M., Heppner, K. M., ... & DiMarchi, R. D. (2013). "Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans". Science Translational Medicine, 5(209), 209ra151. doi:10.1126/scitranslmed.3007218.
- Day, J. W., Gelfanov, V., Smiley, D., Carrington, P. E., Eiermann, G., Chicchi, G., ... & Pocai, A. (2012). "Optimization of co-agonism at GLP-1 and glucagon receptors to treat diabesity". Cell Metabolism, 16(3), 338-349. doi:10.1016/j.cmet.2012.07.007.
- Patel, V. J., & Jones, P. H. (2008). "Glucagon-like peptide 1 receptor agonists for type 2 diabetes". Current Opinion in Endocrinology, Diabetes, and Obesity, 15(2), 169-174. doi:10.1097/MED.0b013e3282f4b6f2.