Feasibility of Transport of 26 Biologically Active Ultrashort Peptides via LAT and PEPT Family Transporters

Khavinson VK, Linkova NS, Rudskoy AI, Petukhov MG · Biomolecules

Against all 8,400 possible di- and tripeptides, the 26 active peptides scored better at LAT1, LAT2 and PEPT1 but not at PEPT2, which the paper names as the exception: thirteen of the twenty-six score positive there — unfavourable — among them EDR and AEDR. AED itself ranked mid-pack among the 26, 14th at LAT1, 12th at LAT2, 13th at PEPT1 and 7th at PEPT2, and the peptides the paper names as the most effective ligands are ED, DS, DR, EDR, EDG, AEDR, AEDL, KEDP and KEDG plus two peptoids, not AED.

Population

Computational docking of 26 ultrashort peptides, including AED, against LAT1, LAT2, PEPT1 and PEPT2

Intervention

Molecular modelling and ligand docking, benchmarked against all 8400 possible di- and tripeptides

Comparator

Di- and tripeptides with no established biological activity, and known transporter substrates

Limitations

Docking scores are a computed binding estimate, not measured transport; no cell, tissue or plasma measurement was made, and the paper does not address whether an oral dose survives digestion. The 8,400-peptide comparison also turns up many unselected di- and tripeptides scoring as well as or better than the 26, which the paper reports and sets aside on the grounds that nothing is known about their activity. Authored from the institute that developed these bioregulators, under a statement declaring no conflict of interest, with the docking data withheld "due to privacy".