دورية أكاديمية

Unraveling the kinetics and pharmacology of human PepT1 using solid supported membrane-based electrophysiology.

التفاصيل البيبلوغرافية
العنوان: Unraveling the kinetics and pharmacology of human PepT1 using solid supported membrane-based electrophysiology.
المؤلفون: Körner A; Fraunhofer Institute for Cell Therapy and Immunology (IZI), Branch Bioanalytics and Bioprocesses (IZI-BB), Am Mühlenberg 13, 14476 Potsdam, Germany; Institute of Biotechnology, Technische Universität Berlin, Straße des 17. Juni 135, 10623 Berlin, Germany., Bazzone A; Nanion Technologies GmbH, Ganghoferstr. 70a, 80339 Munich, Germany., Wichert M; Fraunhofer Institute for Cell Therapy and Immunology (IZI), Branch Bioanalytics and Bioprocesses (IZI-BB), Am Mühlenberg 13, 14476 Potsdam, Germany; Freie Universität Berlin, Institute of Chemistry and Biochemistry - Biochemistry, 14195 Berlin, Germany., Barthmes M; Nanion Technologies GmbH, Ganghoferstr. 70a, 80339 Munich, Germany., Dondapati SK; Fraunhofer Institute for Cell Therapy and Immunology (IZI), Branch Bioanalytics and Bioprocesses (IZI-BB), Am Mühlenberg 13, 14476 Potsdam, Germany. Electronic address: Srujan.Dondapati@izi-bb.fraunhofer.de., Fertig N; Nanion Technologies GmbH, Ganghoferstr. 70a, 80339 Munich, Germany., Kubick S; Fraunhofer Institute for Cell Therapy and Immunology (IZI), Branch Bioanalytics and Bioprocesses (IZI-BB), Am Mühlenberg 13, 14476 Potsdam, Germany; Freie Universität Berlin, Institute of Chemistry and Biochemistry - Biochemistry, 14195 Berlin, Germany; Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus - Senftenberg, The Brandenburg Medical School Theodor Fontane and the University of Potsdam, Germany.
المصدر: Bioelectrochemistry (Amsterdam, Netherlands) [Bioelectrochemistry] 2024 Feb; Vol. 155, pp. 108573. Date of Electronic Publication: 2023 Sep 16.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 100953583 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-562X (Electronic) Linking ISSN: 15675394 NLM ISO Abbreviation: Bioelectrochemistry Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Amsterdam?] : Elsevier, 2000-
مواضيع طبية MeSH: Symporters*/metabolism, Humans ; Peptide Transporter 1 ; Electrophysiology ; Peptides ; Kinetics
مستخلص: The human Peptide Transporter 1 (hPepT1) is known for its broad substrate specificity and its ability to transport (pro-)drugs. Here, we present an in-depth comprehensive study of hPepT1 and its interactions with various substrates via solid supported membrane-based electrophysiology (SSME). Using hPepT1-containing vesicles, we could not identify any peptide induced pre-steady-state currents, indicating that the recorded peak currents reflect steady-state transport. Electrogenic co-transport of H + /glycylglycine (GlyGly) was observed across a pH range of 5.0 to 9.0. The pH dependence is described by a bell-shaped activity curve and two pK values. K M and relative V max values of various canonical and non-canonical peptide substrates were contextualized with current mechanistic understandings of hPepT1. Finally, specific inhibition was observed for various inhibitors in a high throughput format, and IC50 values are reported. Taken together, these findings contribute to promoting the design and analysis of pharmacologically relevant substances.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Authors AB, MB and NF are employed by Nanion Technologies GmbH, the developer of the SURFE(2)R instruments.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Biosensor; High‐throughput screening (HTS); Membrane transport; Peptide Transporter 1 (PepT1); Pharmacology; Solid Supported Membrane-based Electrophysiology (SSME)
المشرفين على المادة: 0 (Symporters)
0 (Peptide Transporter 1)
0 (Peptides)
تواريخ الأحداث: Date Created: 20230925 Date Completed: 20231127 Latest Revision: 20231127
رمز التحديث: 20231127
DOI: 10.1016/j.bioelechem.2023.108573
PMID: 37748262
قاعدة البيانات: MEDLINE