KPV (Lys-Pro-Val) vs LL-37 (Human Cathelicidin)

KPV (Lys-Pro-Val)

KPV is the tripeptide lysine–proline–valine, corresponding to the last three residues of alpha-melanocyte-stimulating hormone (α-MSH). It lacks the His-Phe-Arg-Trp core sequence through which α-MSH activates melanocortin receptors, so its pharmacology cannot be assumed to match that of the parent hormone. Interest in it follows reports that C-terminal fragments of α-MSH alter inflammatory signalling in cell and animal models. Published studies are mainly in cultured epithelial and immune cells and in mouse models of chemically induced colitis. The literature is small, and human data are scarce.

LL-37 (Human Cathelicidin)

LL-37 is a 37-residue peptide cleaved from hCAP18, the only human cathelicidin; its name refers to its two leading leucines and its length. It is made by neutrophils and by epithelial cells of the skin, gut and airways, and the gene that encodes it is regulated in part by vitamin D. Laboratory studies have examined its activity against bacteria, fungi and some viruses, and its signalling to host immune and epithelial cells. Its research record runs in two directions: it is studied as a host-defence molecule and also as a contributor to inflammatory skin conditions such as psoriasis and rosacea. Most published work is in vitro or in animals, and interventional human studies are few and small.

How KPV (Lys-Pro-Val) acts

How KPV acts has not been settled. Cell studies have reported that it lowers activation of the transcription factor NF-κB and reduces expression of inflammatory cytokines in intestinal epithelial and immune cell lines. In intestinal epithelial cells, uptake through the di- and tripeptide transporter PepT1 has been reported, which would allow it to act inside the cell rather than at a surface receptor. Whether it also signals through melanocortin receptors such as MC1R is disputed, since reports differ and its sequence lacks the usual receptor-binding motif. The mechanistic work is limited and comes largely from cell and rodent models.

How LL-37 (Human Cathelicidin) acts

In dilute aqueous solution LL-37 is largely disordered; on contact with lipid membranes it has been reported to fold into an amphipathic α-helix. Its side chains give it a net charge of about +6 at neutral pH, which draws it to the negatively charged surfaces of bacterial membranes, and it is thought to permeabilise those membranes. It also binds bacterial lipopolysaccharide. On host cells it has been reported to act through several receptors, among them formyl peptide receptor 2 and the P2X7 purinergic receptor, and to transactivate the epidermal growth factor receptor in keratinocytes. Complexes of LL-37 with self-DNA or RNA have been reported to activate Toll-like receptor signalling in dendritic cells, a pathway examined in psoriasis research.

The records side by side

• Type: KPV (Lys-Pro-Val), Tripeptide (alpha-MSH fragment); LL-37 (Human Cathelicidin), Antimicrobial peptide (cathelicidin)
• Length: KPV (Lys-Pro-Val), not recorded; LL-37 (Human Cathelicidin), 37 amino acids
• Molecular weight: KPV (Lys-Pro-Val), not recorded; LL-37 (Human Cathelicidin), 4493 g/mol
• Molecular formula: KPV (Lys-Pro-Val), not recorded; LL-37 (Human Cathelicidin), C205H340N60O53

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.