ArticleMolecular pharmaceutics2017
Chemical Modulation of the Human Oligopeptide Transporter 1, hPepT1.
Article in Molecular pharmaceutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Energetics of substrate transport in proton-dependent oligopeptide transporters.Communications chemistry · 2024Article
- Recognizing the biological barriers and pathophysiological characteristics of the gastrointestinal tract for the design and application of nanotherapeutics.Drug delivery · 2024Review
- Structural basis for antibiotic transport and inhibition in PepT2.Nature communications · 2024Article
- FOCUS on NOD2: Advancing IBD Drug Discovery with a User-Informed Machine Learning Framework.ACS medicinal chemistry letters · 2024Article
- Structural basis for antibiotic transport and inhibition in PepT2, the mammalian proton-coupled peptide transporter.Research square · 2024Article
- Targeting SLC transporters: small molecules as modulators and therapeutic opportunities.Trends in biochemical sciences · 2023Review
- Peptide transporter structure reveals binding and action mechanism of a potent PEPT1 and PEPT2 inhibitor.Communications chemistry · 2022Article
- Cryo-EM Structure of an Atypical Proton-Coupled Peptide Transporter: Di- and Tripeptide Permease C.Frontiers in molecular biosciences · 2022Article
- Cryo-EM structure of PepT2 reveals structural basis for proton-coupled peptide and prodrug transport in mammals.Science advances · 2021Article
- Studies of structural determinants of substrate binding in the Creatine Transporter (CreaT, SLC6A8) using molecular models.Scientific reports · 2020Article
- Toward a Systematic Structural and Functional Annotation of Solute Carriers Transporters-Example of the SLC6 and SLC7 Families.Frontiers in pharmacology · 2020Review
- Advances and Challenges in Rational Drug Design for SLCs.Trends in pharmacological sciences · 2019Review
- Molecular Modeling of Drug-Transporter Interactions-An International Transporter Consortium Perspective.Clinical pharmacology and therapeutics · 2018Review
- Tripeptide binding in a proton-dependent oligopeptide transporter.FEBS letters · 2018Article
- Free Energy Landscape of the Complete Transport Cycle in a Key Bacterial Transporter.ACS central science · 2018Article
- Homology Modeling Informs Ligand Discovery for the Glutamine Transporter ASCT2.Frontiers in chemistry · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
In humans, peptides derived from dietary proteins and peptide-like drugs are transported via the proton-dependent oligopeptide transporter hPepT1 (SLC15A1). hPepT1 is located across the apical membranes of the small intestine and kidney, where it serves as a high-capacity low-affinity transporter of a broad range of di- and tripeptides. hPepT1 is also overexpressed in the colon of inflammatory bowel disease (IBD) patients, where it mediates the transport of harmful peptides of bacterial origin. Therefore, hPepT1 is a drug target for prodrug substrates interacting with intracellular proteins or inhibitors blocking the transport of toxic bacterial products. In this study, we construct multiple structural models of hPepT1 representing different conformational states that occur during transport and inhibition. We then identify and characterize five ligands of hPepT1 using computational methods, such as virtual screening and QM-polarized ligand docking (QPLD), and experimental testing with uptake kinetic measurements and electrophysiological assays. Our results improve our understanding of the substrate and inhibitor specificity of hPepT1. Furthermore, the newly discovered ligands exhibit unique chemotypes, providing a framework for developing tool compounds with optimal intestinal absorption as well as future IBD therapeutics against this emerging drug target.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.