LY3437943 Reference
Written by the Pure Peptides editorial team
Molecular Profile
Compound
LY3437943
Also known as
Pure-RTA-3
CAS number
2381089-83-2
UNII
NOP2Y096GV
Molecular formula
C221H342N46O68
Molecular weight
4731.3 g/mol (average)
Amino acid sequence
Y-Aib-Q-G-T-F-T-S-D-Y-S-I-αMeL-L-D-K-K*-A-Q-Aib-A-F-I-E-Y-L-L-E-G-G-P-S-S-G-A-P-P-P-S-NH2 (39 residues)
Side-chain modification
lysine 17 carries one AEEA unit, then γ-glutamic acid, then eicosanedioic acid
Purity
99%
Physical form
Lyophilized powder
What LY3437943 is, structurally
LY3437943 is a 39-residue peptide carrying a C-terminal amide, two alpha,alpha-disubstituted residues, and a fatty-acid chain attached through the side chain of lysine 17. The fatty acid changes it most.
The specification is internally consistent, which is worth confirming rather than assuming. Rebuilding the formula from the stated sequence and modifications gives C221H342N46O68 at 4731.4 against a stated 4731.3. The nitrogen count reconciles too: 39 backbone nitrogens (38 peptide-bond amides and the free N-terminal amine), one C-terminal amide, four on side chains from two lysines and two glutamines, and two in the linker, one in the AEEA unit and one in the gamma-glutamic acid. That is 46, exactly as stated.
The alpha,alpha-disubstituted residues are easy to overlook. Aib sits at positions 2 and 20, alpha-methyl-leucine at position 13. Each carries two substituents on the alpha-carbon rather than one, so neither has an alpha-hydrogen, and removing that hydrogen removes the route by which a residue epimerizes, since base-catalyzed racemization proceeds by abstracting it. Aib goes further: bearing two identical methyls, it has no stereocenter at the alpha-carbon at all. Both positions also restrict backbone rotation.
The acyl chain is the dominant handling fact. A twenty-carbon diacid, joined through gamma-glutamic acid and an AEEA spacer to lysine 17, gives an otherwise hydrophilic peptide a long hydrophobic tail, and amphiphiles do not behave in solution as peptides do.
Three consequences follow. Amphiphiles aggregate above a threshold concentration, so a concentrated stock and a dilute working solution may differ in what they contain. A hydrophobic tail also partitions onto plastic and glass, so losses at low concentration can be substantial rather than a trace. And the diacid's far end matters: only one of its two carboxyls forms the amide to gamma-glutamic acid, leaving the other free and negatively charged at neutral pH, and the gamma-glutamic acid keeps a free carboxyl of its own. Added to the two aspartates and two glutamates in the sequence, that makes the molecule distinctly acidic, so solubility improves toward neutral and mildly alkaline pH.
Two weak points are visible in the sequence. Three tyrosines are oxidation-prone, and two glutamines can deamidate to glutamate, adding about one mass unit each. There is no cysteine and no methionine, so no disulfide chemistry and no sulfoxide route.
Structure at a glance
Pure-RTA-3: C 221, N 46, O 68.
Drawn from the product database.
Reconstitution and handling
Sterile water is the usual starting solvent, and neutral to mildly alkaline buffers suit an acidic, acylated peptide. Dilute acid, which helps many peptides dissolve, works against this one.
Add diluent slowly down the inside wall of the vial and swirl gently. Do not vortex; a surface-active molecule foams readily, and foam is an air-liquid interface rather than a cosmetic problem.
Use low-binding tubes and keep transfers few, for the adsorption reason above.
No reducing agent is needed, since the formula contains no sulfur.
This is laboratory preparation chemistry, not dosing, administration, or protocol guidance of any kind.
Storage and stability
Store the lyophilized powder at -20 degrees C, sealed, desiccated and protected from light, and let a cold vial warm before opening. Reconstituted, hold at 2 to 8 degrees C, or aliquot and freeze rather than thawing repeatedly.
Tyrosine oxidation is the named chemical liability, accelerated by air, warmth and light. Glutamine deamidation is the second, needs water, and is accelerated by warmth and alkaline pH, which is the one argument against holding solutions alkaline for long.
Aggregation deserves separate mention because it is physical rather than chemical and no mass measurement reports it. Associated material may not redisperse on dilution, and freeze-thaw promotes it, which is the practical reason to aliquot on first reconstitution.
These are storage conditions for the material, not dosing or administration guidance.
How LY3437943 is tested
Reversed-phase HPLC establishes chromatographic purity as area percent, and the acyl chain shifts expectations. A twenty-carbon tail retains strongly on a C18 column, so a higher organic proportion is needed than for an unmodified peptide of this length.
Detection sits near 214 nm, and the three tyrosines give usable absorbance near 280 nm as well.
Area percent is a chromatographic measure, not peptide content by weight: water and counter-ions also add to the weight of the powder.
Mass spectrometry confirms identity against 4731.3. At this size average and monoisotopic figures differ appreciably, so establish the reporting basis before comparing against the label. Sixteen units indicates oxidation, one unit deamidation; loss of the acyl side chain would be far larger and unmistakable.
These describe general methodology, not a claim about any particular batch.
Handling FAQ
Why do low-binding tubes matter more for this compound than for an ordinary peptide?+−
Because of the fatty-acid chain. A long hydrophobic tail partitions onto plastic and glass, so at low working concentration the loss can be a large fraction rather than a trace.
Should dilute acid be used to help a slow vial dissolve?+−
Not here. The free carboxyls on the diacid and the gamma-glutamic acid, with the two aspartates and two glutamates in the sequence, make this molecule acidic overall, so lowering the pH moves it toward poorer solubility. Neutral to mildly alkaline conditions are the right direction. Full specifications for Pure-RTA-3.
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