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Review
. 2023 Oct 23;15(10):2517.
doi: 10.3390/pharmaceutics15102517.

Molecular Insights to the Structure-Interaction Relationships of Human Proton-Coupled Oligopeptide Transporters (PepTs)

Yining Luo  1 , Jingchun Gao  1 , Xukai Jiang  2 , Ling Zhu  3 , Qi Tony Zhou  4 , Michael Murray  1 , Jian Li  5 , Fanfan Zhou  1
Affiliations
Review

Molecular Insights to the Structure-Interaction Relationships of Human Proton-Coupled Oligopeptide Transporters (PepTs)

Yining Luo et al. Pharmaceutics. .

Abstract

Human proton-coupled oligopeptide transporters (PepTs) are important membrane influx transporters that facilitate the cellular uptake of many drugs including ACE inhibitors and antibiotics. PepTs mediate the absorption of di- and tri-peptides from dietary proteins or gastrointestinal secretions, facilitate the reabsorption of peptide-bound amino acids in the kidney, and regulate neuropeptide homeostasis in extracellular fluids. PepT1 and PepT2 have been the most intensively investigated of all PepT isoforms. Modulating the interactions of PepTs and their drug substrates could influence treatment outcomes and adverse effects with certain therapies. In recent studies, topology models and protein structures of PepTs have been developed. The aim of this review was to summarise the current knowledge regarding structure-interaction relationships (SIRs) of PepTs and their substrates as well as the potential applications of this information in therapeutic optimisation and drug development. Such information may provide insights into the efficacy of PepT drug substrates in patients, mechanisms of drug-drug/food interactions and the potential role of PepTs targeting in drug design and development strategies.

Keywords: drug development; drug optimisation; proton-coupled oligopeptide transporters; structure-interaction relationships.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Transport mechanisms of PepT1 and PepT2 in intestinal epithelial cells. Key: CaSR: calcium sensing receptor; Gly-Sar: glycylsarcosine; PLC: phospholipase C; NHE3: Na+/H+ exchanger 3.
Figure 2
Figure 2
Transport mechanisms of PepT1 and PepT2 in renal tubular cells.
Figure 3
Figure 3
Predicted topology model of PepTs. Numbers in the figure indicate the predicted 12 transmembrane domains.
See this image and copyright information in PMC

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