Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers

Abstract

Ultrashort peptides (USPs), consisting of 2–7 amino-acid residues, are a group of signaling molecules that regulate gene expression and protein synthesis under normal conditions in various diseases and ageing. USPs serve as a basis for the development of drugs with a targeted mechanism of action. The purpose of this review is to systematize the available data on USP transport involving POT and LAT transporters in various organs and tissues under normal, pathological and ageing conditions. The carriers of the POT family (PEPT1, PEPT2, PHT1, PHT2) transport predominantly di- and tripeptides into the cell. Methods of molecular modeling and physicochemistry have demonstrated the ability of LAT1 to transfer not only amino acids but also some di- and tripeptides into the cell and out of it. LAT1 and 2 are involved in the regulation of the antioxidant, endocrine, immune and nervous systems’ functions. Analysis of the above data allows us to conclude that, depending on their structure, di- and tripeptides can be transported into the cells of various tissues by POT and LAT transporters. This mechanism is likely to underlie the tissue specificity of peptides, their geroprotective action and effectiveness in the case of neuroimmunoendocrine system disorders.

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

“… * Preliminary results of USP docking at the LAT1 active site are presented in a recently published review of the literature on the structure and biological activity of the LAT and POT family transporters [ 4 ]. The data obtained in this work differ somewhat from preliminary calculations due to the use of several different conformations of the LAT1 active site, which is observed in various LAT1 structures available in PDB (PDB ID: 6IRS), as well as the use of new, more advanced techniques for docking mobile ligands with increased thoroughness.…”

“…USPs are assumed to enter the cell with the participation of proton-dependent oligopeptide transporters (POT) [ 4 ]. The transport of USPs with the length of 2–3 amino acid residues can also be carried out with the participation of L-type amino acid transporters (LAT1 and LAT2).…”

“…The transport of USPs with the length of 2–3 amino acid residues can also be carried out with the participation of L-type amino acid transporters (LAT1 and LAT2). These amino acid transporters and USPs are essential for the nutrient supply of the cell, recycling of neurotransmitters, maintenance of redox balance, and intracellular signaling [ 4 ].…”

Circulating (poly)phenol metabolites in the brain: unveiling in vitro and in vivo blood-brain barrier transport

“…Aiming to further dissect this possibility, we studied the expression and possible contribution that the most transported metabolite, Pyr-sulf, may have to different SLC transporters. Considering the most documented CMT and RMT at BBB level, we tested 25 transporter candidates for HBMEC [34][35][36][37]. Surprisingly, Pyr-Sulf significantly downregulated four CMT, ASCT1/SLC1A4, CAT1/SLC7A1, OATP1A2/SLCO1A2 at mRNA and protein level and SNAT2/SLC38A2 at mRNA level.…”

“…We performed a literature revision of the most representative carrier-mediated (CMT) and receptor-mediated transporters (RMT) predicted to be present in brain microvascular endothelial cells [34][35][36][37][38] (Figure 4A). To assure which major BBB transporters are expressed in the HBMEC line, a RT-qPCR was performed.…”