KPV Peptide: Sequence, Structure and Lab Data

The KPV peptide is the tripeptide Lys-Pro-Val (one-letter sequence KPV), the last three residues, 11 to 13, of the 13-residue peptide alpha-melanocyte-stimulating hormone (alpha-MSH). As a free acid it has the formula C16H30N4O4 and an average mass of 342.43 g/mol (monoisotopic 342.227 Da), CAS 67727-97-3, PubChem CID 125672. Several related forms share the name, most often the capped Ac-KPV-NH2 (383.5 g/mol), so the termini matter when comparing papers or lots. PubMed holds roughly 50 records on the tripeptide, mostly cell-based and rodent work, and none is indexed as a clinical trial.

KPV peptide at a glance

Source: PubChem CID 125672 (formula, masses, CAS synonym); charge counted from the ionisable groups; reference 1 for the parent sequence.

Research materials: Vortex supplies KPV as a lyophilised research reagent: KPV peptide 10mg. Lab reports: /coa/.

What is the KPV peptide? Its place in alpha-MSH

Alpha-MSH is a 13-residue peptide with the sequence Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2. Harris and Lerner reported its amino-acid sequence in 1957 [1]. Its sequence matches residues 1 to 13 of ACTH, so KPV also appears in catalogues as “ACTH (11-13)”. KPV is residues 11 to 13: lysine, proline, valine.

Two details separate KPV from the same three residues inside alpha-MSH. In the parent peptide, the valine at position 13 ends in an amide (-NH2), and the lysine at position 11 is joined to glycine 10 by a peptide bond. Free KPV has a carboxylic acid at the valine end and a free amine at the lysine end. Those ends change the charge, mass and chromatography, so “KPV” alone does not fully define a material. Our explainer on what peptides are covers how termini and peptide bonds are written.

History: how a three-residue fragment got its own literature

The interest in KPV as a separate molecule began with structure-activity work on alpha-MSH. In 1976, Eberle and Schwyzer measured the in vitro receptor-mediated activity of 24 synthetic alpha-MSH-related peptides. They found that the C-terminal tripeptide (11-13), tetrapeptide (10-13) and pentapeptide (9-13) were active on their own, in the same order of magnitude as the central hexapeptide (5-10). They concluded that alpha-MSH carries two separate “message sequences”, the central -Glu-His-Phe-Arg-Trp- and the C-terminal -Gly-Lys-Pro-Val-NH2 [2].

In 1984, Cody, Hruby and colleagues reported that in cyclic alpha-MSH analogues Lys11 and Pro12 contributed to potency in three in vitro bioassays, and Val13 to a lesser extent [3]. From the late 1980s, the isolated free-acid tripeptide became a research subject in its own right, with much of the early pharmacology from James M. Lipton’s laboratory. The record is still small: a PubMed title-and-abstract search for KPV with “peptide”, “tripeptide” or “MSH” returns about 50 records (1 November 2026). Adding “Lys-Pro-Val” and “alpha-MSH (11-13)” raises that to about 150, including some unrelated uses of the abbreviation.

KPV peptide sequence and its variants

The KPV peptide sequence is written Lys-Pro-Val or KPV, N-terminus first. Papers and suppliers use at least five related molecules under similar names. Three of them differ in their termini, one differs only in the handedness of one residue, and one is a different tripeptide altogether.

Source: PubChem CIDs 125672, 9209049 and 159483; H-KPV-NH2 calculated from CID 125672 by replacing the C-terminal OH with NH2.

Ac-KPV-NH2 is the form closest to the way residues 11 to 13 sit inside alpha-MSH: the acetyl group stands in for the peptide bond to glycine 10, and the amide matches the parent C-terminus. Chavatte and colleagues used this capped form in a molecular dynamics study, sorting its conformations into families on the phi-psi map and using the most stable member of each as a template for six constrained non-peptide designs [6].

Two of the rows are traps for identity testing. KP-D-V has exactly the same formula and mass as KPV, so mass spectrometry cannot tell them apart; only a chiral method or a comparison with authentic standards of each isomer can. KdPT is a different molecule whose mass is only 2 Da higher than KPV’s. It is a separate tripeptide, and its data do not transfer to KPV.

Databases add one more trap: a PubChem name lookup for “KPV” resolves to an unrelated small molecule, 2-oxo-5-phenylpentanoic acid (CID 13294447). Quote the CAS number 67727-97-3 or CID 125672 instead.

Synthesis and salt forms of KPV

KPV is made by standard solid-phase peptide synthesis. Cleavage from the resin and reversed-phase purification both use trifluoroacetic acid, so peptides with basic groups usually leave purification as trifluoroacetate (TFA) salts. Roux and colleagues compared ways to remove or exchange the TFA ion and found that reversed-phase HPLC and ion-exchange resin could swap it, partly to almost completely, for the counter-ion of a weaker acid such as acetate [7]. A review of peptide counter-ions notes that the counter-ion affects a peptide’s structure and physicochemical properties [8]. PubChem’s synonym list for CID 125672 includes “H-Lys-Pro-Val-OH acetate salt”, the form most catalogues list.

KPV has two amines that can be protonated, the N-terminal amine and the lysine side chain, so a fully formed salt carries up to two counter-ions per molecule. Because KPV is so small, the counter-ion is a large share of the solid’s mass, much larger than for a 15-residue peptide.

Source: calculated from standard atomic masses (acetic acid 60.05 g/mol, trifluoroacetic acid 114.02 g/mol). Residual water, which every lyophilised solid also holds, is left out.

A fully formed di-TFA solid is only about 60% peptide by mass, so a directly measured net content matters more for KPV than for most larger peptides.

Stability chemistry: diketopiperazine formation

KPV has a proline in position 2, and peptides with proline second from the N-terminus are prone to one particular reaction. The free N-terminal amine can attack the carbonyl of the second peptide bond, closing a six-membered ring and releasing the rest of the chain. The ring is a 2,5-diketopiperazine (DKP).

Dipeptide sequences with proline in the second position can cyclise to a diketopiperazine, and the rate depends on the residues and on pH [9]. In KPV the Lys-Pro end is that motif. For KPV, that reaction releases valine and leaves cyclo(Lys-Pro), C11H19N3O2, monoisotopic mass 225.148 Da.

Work on model peptides explains why the reaction depends on pH. Goolcharran and Borchardt followed DKP formation from a Phe-Pro model peptide and found pseudo-first-order kinetics that depended on the ionisation of the N-terminal amine: the unprotonated amine reacted faster than the protonated one. The residue before proline also changed the rate [9]. In a dry lyophilised solid, with little water and no buffer, this chemistry is generally slower than in solution. Our explainer on storing lyophilised peptides covers sealed-solid storage.

Cell- and molecule-level findings

This section covers only measurements made in cell lines or cell-free systems.

Melanocortin-1 receptor and second-messenger signalling

Elliott and colleagues compared signalling by alpha-MSH, KPV, KP-D-V and ACTH peptides in the HaCaT keratinocyte line and in normal human keratinocytes. They detected no rise in cyclic AMP in either cell type with any of the peptides. They did record rapid intracellular calcium signals in HaCaT cells with alpha-MSH, KPV and KP-D-V, but only when an adenosine agonist that inhibits the cyclic AMP pathway was present. In Chinese hamster ovary cells stably transfected with the melanocortin-1 receptor (MC1R), alpha-MSH and both KPV peptides raised intracellular calcium [5]. In these cells the signal recorded was calcium, not cyclic AMP, for the full peptide and the tripeptide alike.

Lysine modification and protease stability

Songok and colleagues developed a “glycoalkylation” of lysine amines, which turns the amine into a dihydroxylated piperidine, and applied it to H-KPV-NH2 to make alpha- and epsilon-modified analogues. The glycoalkylated peptides showed stability toward proteolytic enzymes [4].

Where the data stop

Most of the remaining literature is rodent pharmacology from a small number of laboratories. No PubMed record for KPV is indexed as a clinical trial, and no controlled human study of the tripeptide has been published.

Analytical verification of a KPV lot

A KPV lot is verified by mass spectrometry for identity and HPLC for purity.

Identity by mass spectrometry

Electrospray ionisation produces protonated, often multiply charged, ions from peptides [10]. For free KPV, expect [M+H]⁺ at m/z 343.234. The doubly protonated ion, [M+2H]²⁺, sits at m/z 172.121, because KPV has two basic amines. Ac-KPV-NH2 gives [M+H]⁺ at m/z 384.261, and H-KPV-NH2 at m/z 342.250, only about 1 Da below free KPV’s ion. A signal at m/z 226.155 points to the cyclo(Lys-Pro) degradation product. MS confirms the mass. It cannot separate KPV from KP-D-V, and it does not show the salt form, because the counter-ion separates from the peptide in the source. Our explainer on LC-MS peptide analysis covers how these ions are read.

Source: monoisotopic masses from PubChem (KPV, Ac-KPV-NH2, KdPT) or calculated from formula; proton mass 1.00728 Da.

Purity by HPLC

KPV is small and basic, so on reversed-phase HPLC it elutes early under acidic conditions, where peak integration is least reliable. Retention and selectivity for peptides depend heavily on column chemistry and organic solvent [11], so a method has to be checked for separation of KPV from its diketopiperazine. A purity figure counts peptide-related impurities as a share of UV peak area. It does not measure counter-ion or water. Our explainer on HPLC peptide purity covers what the number means.

Checking a lot of KPV

Vortex publishes lab reports at /coa/. The KPV 10 mg product currently has one published report, lot PS07-KPV10. It is a partner-facility report: ILS Laboratories (San Diego, CA) issued it to Vortex’s wholesale partner facility, and it covers the batch Vortex stocks. It is not a Vortex-name report.

Source: the PS07-KPV10 card on /coa/ and the KPV product page, read 1 November 2026. The report can be looked up on the lab’s portal with the access code shown on /coa/.

Identity on this report is by HPLC, not mass spectrometry, so the m/z values above are what an MS identity test would be expected to show, not results from this report. The 10.66 mg net content is the figure the lab reports for the vial; the report page describes its analysis as RP-HPLC with UV detection and does not name a counter-ion form. For the KLOW blend, which contains 10 mg of KPV, no lot report has been published yet. Our KLOW peptide reference covers the blend’s composition, and our explainer on reading a peptide COA covers each field of a report.

Frequently asked questions

Is KPV the same as alpha-MSH?

No. KPV is the three-residue C-terminal fragment of alpha-MSH, residues 11 to 13 (Lys-Pro-Val). Alpha-MSH has 13 residues, an acetylated N-terminus and an amidated C-terminus, while free KPV has a free amine and a free carboxylic acid.

What is the molecular weight of KPV?

Free KPV (C16H30N4O4) has an average molecular weight of 342.43 g/mol and a monoisotopic mass of 342.227 Da. The capped form Ac-KPV-NH2 is 383.5 g/mol. Salt forms weigh more per peptide molecule: a di-acetate is about 462.5 g/mol.

What is the KPV peptide sequence?

The sequence is lysine-proline-valine, written Lys-Pro-Val or KPV from the N-terminus. In the standard free-acid form all three residues are L-amino acids. KP-D-V has the same sequence with D-valine and the same mass.

Is Ac-KPV-NH2 the same compound as KPV?

No. Ac-KPV-NH2 has an acetyl group on the N-terminus and an amide at the C-terminus. It has the formula C18H33N5O4, a mass of 383.5 g/mol and its own PubChem record, CID 9209049. Mass spectrometry distinguishes it easily from free KPV.

Has KPV been studied in humans?

No PubMed record for KPV is indexed as a clinical trial, and no controlled human study of the tripeptide has been published. The literature is mostly cell-line, cell-free and rodent work, plus analytical and synthetic chemistry papers.

Research materials: KPV peptide 10mg is supplied as a lyophilised research reagent. Published lab reports are at /coa/.

About this article: Written by the Vortex Research Editorial Team. Sources are peer-reviewed papers indexed in PubMed, each checked for title, journal and year and matched to its abstract. Formulas and masses are from PubChem; m/z values are calculated from the formulas. Lab report figures are from the published reports at /coa/.

References

1. Harris JI, Lerner AB. Amino-acid sequence of the alpha-melanocyte-stimulating hormone. Nature. 1957;179(4574):1346-1347. PMID 13451616
2. Eberle A, Schwyzer R. Hormone-receptor interactions. The message sequence of alpha-melanotropin: demonstration of two active sites. Clin Endocrinol (Oxf). 1976;5 Suppl:41S-48S. PMID 212233
3. Cody WL, Wilkes BC, Muska BJ, Hruby VJ, Castrucci AM, Hadley ME. Cyclic melanotropins. 5. Importance of the C-terminal tripeptide (Lys-Pro-Val). J Med Chem. 1984;27(9):1186-1190. PMID 6332195
4. Songok AC, Panta P, Doerrler WT, Macnaughtan MA, Taylor CM. Structural modification of the tripeptide KPV by reductive “glycoalkylation” of the lysine residue. PLoS One. 2018;13(6):e0199686. PMID 29953505
5. Elliott RJ, Szabo M, Wagner MJ, Kemp EH, MacNeil S, Haycock JW. alpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells. J Invest Dermatol. 2004;122(4):1010-1019. PMID 15102092
6. Chavatte P, Yous S, Lesieur D, Hénichart JP. Conformational analysis of tripeptide Ac-Lys-Pro-Val-NH2, COOH-terminal sequence of alpha-MSH. J Pharm Pharmacol. 2001;53(7):949-953. PMID 11480545
7. Roux S, Zékri E, Rousseau B, Paternostre M, Cintrat JC, Fay N. Elimination and exchange of trifluoroacetate counter-ion from cationic peptides: a critical evaluation of different approaches. J Pept Sci. 2008;14(3):354-359. PMID 18035848
8. Sikora K, Jaśkiewicz M, Neubauer D, Migoń D, Kamysz W. The role of counter-ions in peptides: an overview. Pharmaceuticals (Basel). 2020;13(12):442. PMID 33287352
9. Goolcharran C, Borchardt RT. Kinetics of diketopiperazine formation using model peptides. J Pharm Sci. 1998;87(3):283-288. PMID 9523979
10. Fenn JB, Mann M, Meng CK, Wong SF, Whitehouse CM. Electrospray ionization for mass spectrometry of large biomolecules. Science. 1989;246(4926):64-71. PMID 2675315
11. Mant CT, Cepeniene D, Hodges RS. Reversed-phase HPLC of peptides: assessing column and solvent selectivity on standard, polar-embedded and polar endcapped columns. J Sep Sci. 2010;33(19):3005-3021. PMID 21038458

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