KPV peptide research reference: CAS, molecular weight, sequence, solubility and handling

Alpha-MSH is a 13-residue peptide cut from pro-opiomelanocortin. In the 1980s and 1990s several groups noticed that its C-terminal three residues, Lys-Pro-Val, kept part of the parent hormone's activity in inflammation models, even though the tripeptide lacks the central His-Phe-Arg-Trp sequence that most melanocortin receptor binding depends on. That made KPV a tool for asking which effects need the melanocortin receptors and which do not (Brzoska et al., 2008; Luger and Brzoska, 2007).

Later work in mouse models found that KPV is a substrate of PepT1, the intestinal di- and tripeptide transporter, and that its effects in cells expressing PepT1 depended on that uptake (Dalmasso et al., 2008). All of this is preclinical. KPV is not an approved drug.

KPV is about as simple as peptides get: three residues, no aromatic side chain, no sulfur and no aspartate or asparagine. It has no strong UV chromophore apart from the peptide bonds, so HPLC detection has to use low wavelengths (around 210 to 220 nm), where buffer and solvent impurities also absorb. Keep that in mind when you read a purity figure.

The one sequence feature to watch is the proline in position 2. Peptides with Pro (or Gly) second from the free N-terminus can cyclize: the N-terminal amine attacks the second peptide bond and releases a diketopiperazine, here cyclo(Lys-Pro), leaving free valine. Model-peptide studies show this reaction depends on pH and temperature and can be significant in solution (Goolcharran and Borchardt, 1998). For KPV the practical result is a loss of parent peptide that a purity trace would show as new early-eluting peaks.

With a lysine, a free amine and a free carboxylate, KPV is net positive and very polar at neutral pH. Water dissolves it readily at typical stock concentrations. If a lot is supplied as an acetate or TFA salt, it may already be slightly acidic in solution, which is fine for dissolution. Charge-based guides such as GenScript's recommend water first for a basic, short peptide like this, with dilute acetic acid as the fallback.

1. Equilibrate the closed vial to room temperature before opening.
2. Add water down the side of the vial and swirl; KPV should clear within seconds.
3. Avoid holding stocks at elevated temperature or high pH, which favour diketopiperazine formation.
4. Record solvent, volume, pH and date.

Store the lyophilized powder sealed at -20 C or below, with desiccant. Short peptides are hygroscopic, and moisture both changes the weighed mass and enables the cyclization reaction described above. In solution, keep stocks cold, split them into single-use aliquots and freeze them. Because the degradation product is cyclo(Lys-Pro) plus valine, an old stock can look clear and still have lost parent peptide. Date every aliquot, and don't trust appearance.

For a tripeptide, identity by mass is quick and cheap, so it is reasonable to expect it. The protonated ion should sit at m/z 343.2. Because KPV absorbs weakly in the UV, also check the detection wavelength on any HPLC purity figure.

1. Lot number matching the vial, lab name and a lookup route.
2. HPLC purity with the wavelength and the chromatogram.
3. Mass near m/z 343.2. A peak near m/z 226.2 would fit cyclo(Lys-Pro), the diketopiperazine.
4. Measured quantity or net peptide content.
5. The correct CAS (67727-97-3) and formula (C16H30N4O4).

We list KPV in a 10 mg vial for laboratory research. We do not yet have a published third-party lot report for KPV, so we do not show one here. A lot report is available on request through the testing page, and we will add it to the COA dataset only when a report issued for our lot is in hand.