FOXO4-DRI (Proxofim)

What FOXO4-DRI is, structurally

FOXO4-DRI is a D-retro-inverso peptide, and the product page states as much in its own copy: the residue order is reversed and every residue is the D enantiomer rather than the L form.

A retro-inverso peptide has the same molecular formula and molecular weight as the all-L sequence it was modelled on. It is a stereochemical variant, not a compositional one, and the consequence is easily missed: mass spectrometry cannot tell the two apart. A correct mass establishes composition and stops there.

Chromatography does separate them: a partly inverted chain is a diastereomer of the fully inverted one, and diastereomers, unlike enantiomers, resolve on an ordinary reversed-phase column. Circular dichroism distinguishes them too, giving signals of opposite sign for D and L. The reasoning is that of the disulfide-scrambling problem on the cysteine-containing products, the identity test most readers trust being the one blind to the failure, and the exposure is wider here, since every chiral residue is such a centre.

Formula and sequence are both empty at source, and the public record does not close the gap: the peptide recorded under this CAS computes some nineteen units below the stated 5377, so it cannot stand as this product's specification and nothing residue-level rests on it. The stated weight does imply a size, roughly 45 to 48 residues at ordinary average residue mass, as an inference rather than a datum.

Two leads follow from that record, their standing attached. It carries no sulfur, which if true here closes disulfide bonding, thiol oxidation and methionine sulfoxide, and its nitrogen count suits an arginine-rich chain. Neither is settled while the weights disagree.

Reconstitution and handling

Sterile water is the default solvent. The product page describes a second, positively charged segment appended to the chain, and a strongly cationic peptide should dissolve readily.

Add diluent slowly down the inside wall of the vial, swirl gently, and let the solution clarify. Do not vortex. Where a vial resists, mildly acidic conditions raise the net positive charge and assist.

Buffer choice deserves care, since alkaline conditions catalyse racemisation and identity here rests on configuration at every chiral residue. Neutral to mildly acidic is safer.

A peptide carrying this much positive charge also binds negatively charged surfaces, so at low concentration borosilicate glass is a poor choice and low-protein-binding polypropylene better.

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 so moisture does not condense onto it. Reconstituted, hold at 2 to 8 degrees C, or aliquot and freeze rather than thawing repeatedly.

Epimerisation is the liability specific to this molecule. Racemisation is base-catalysed and heat-accelerated, so alkaline conditions and warmth are what to avoid and near-neutral cold storage is the control. Detection is the awkward part: the epimer has the same mass as the starting material, so a stability study resting on mass alone will not see it. A chromatographic profile will.

Desiccation matters more than average, since heavily charged lyophilized material takes up moisture quickly once opened.

These are storage conditions for the material, not dosing or administration guidance.

How FOXO4-DRI is tested

The product page states HPLC and MS-UPLC. Reversed-phase HPLC establishes chromatographic purity as area percent, and here it carries unusual weight, being the method able to resolve the impurity mass spectrometry cannot.

Greater than 99 percent is demanding on a chain of this length. Long solid-phase syntheses accumulate deletion and truncation products from incomplete couplings; those shift the mass, so mass spectrometry sees them. Epimers it does not.

A further stereochemical question sits outside both methods: the enantiomeric purity of the D-configured building blocks, since contamination at monomer level propagates into the product. Chiral analysis of the hydrolysate answers that, not chromatography of the intact chain.

Area percent is a chromatographic measure rather than peptide content by weight, and the counter-ion burden on a strongly basic peptide is substantial; the page states that labelled quantity is net peptide content.

At around 5.4 kilodaltons the isotope envelope is broad and the monoisotopic peak is not the tallest, so the two mass conventions differ and should not be conflated.

These describe general methodology, not a claim about any particular batch.

Handling FAQ

Will a mass spectrum confirm this material has the right stereochemistry? No. Retro-inverso construction changes residue order and configuration, not composition, so the all-D peptide and its all-L counterpart share a formula and a mass. Chromatography separates diastereomers, and circular dichroism distinguishes D from L by the sign of the signal.

The weight is given as approximately 5,377. Is the exact value known? Not from the product database, which carries no formula. The peptide recorded under this CAS computes some nineteen units lower, and because the two disagree this page reports the supplied figure and flags the gap.

Full specifications for FOXO4-DRI (Proxofim).