Retatrutide

Retatrutide is a synthetic 39-residue peptide of molecular formula C₂₂₁H₃₄₂N₄₆O₆₈, with an average molecular mass of 4731.42 Da and a monoisotopic mass of 4728.4718 Da. The chain opens Tyr-Aib-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr and closes Gly-Ala-Pro-Pro-Pro-Ser, the C-terminus being an amide rather than a free acid. Three positions depart from the twenty proteinogenic amino acids: alpha-aminoisobutyric acid occupies positions 2 and 20, and an alpha-methylated leucine occupies position 13. These alpha,alpha-disubstituted residues are introduced during solid-phase assembly and are resolved analytically by their mass increments relative to the corresponding proteinogenic residues.

A single lipid substituent is carried on the epsilon-amine of Lys17. It comprises an eicosanedioic (C20 alpha,omega-dicarboxylic) acyl group joined through a gamma-glutamate spacer and one 2-[2-(2-aminoethoxy)ethoxy]acetyl (AEEA) unit, contributing C₃₁H₅₄N₂O₉ to the intact formula. The unmodified 39-residue backbone corresponds to C₁₉₀H₂₈₈N₄₄O₅₉; the difference between that composition and the intact molecular formula is the diagnostic signature of the acyl-spacer assembly, and reconstructing it from the sequence reproduces the deposited formula exactly.

The compound sits among the incretin-family peptide analogues built on the glucagon/secretin peptide fold. Three receptor entries are named against it: the gastric inhibitory polypeptide receptor (UniProt P48546), the glucagon-like peptide 1 receptor (UniProt P43220) and the glucagon receptor (UniProt P47871).

Retatrutide is distinguished from tirzepatide, its closest structural relative, on four counts: the acyl chain is attached at Lys17 rather than Lys20; the spacer carries one AEEA unit rather than two; position 13 is alpha-methyl-leucine rather than alpha-aminoisobutyric acid; and the segment spanning positions 23 to 28 reads Ile-Glu-Tyr-Leu-Leu-Glu in place of Val-Gln-Trp-Leu-Ile-Ala. The two compositions differ by C₄H₆N₂, a separation of 82.11 Da in average mass that is unambiguous by electrospray mass spectrometry.

This material is supplied strictly for in-vitro laboratory research. It is not a drug, food or supplement, and is not for human or veterinary use, diagnosis, or consumption.