The prototypical oligopeptide transporter YdgR from E. coli exhibits a strict preference for β-Ala-Lys(AMCA)

Salvia Sajid; Cecilia Ninh; Ruyu Yan; Maria  Raﬁq; Lars Porskjær Christensen; Mikkel Girke Jørgensen; Paul Robert Hansen; Henrik Franzyk; Osman Mirza; Bala Krishna Prabhala

doi:10.1002/psc.3670

The prototypical oligopeptide transporter YdgR from E. coli exhibits a strict preference for β-Ala-Lys(AMCA)

Salvia Sajid, Cecilia Ninh, Ruyu Yan, Maria Raﬁq, Lars Porskjær Christensen, Mikkel Girke Jørgensen, Paul Robert Hansen, Henrik Franzyk, Osman Mirza, Bala Krishna Prabhala^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

Fluorescent probes are widely used in cellular imaging and disease diagnosis. Acting as substitute carriers, fluorescent probes can also be used to help transport drugs within cells. In this study, commonly used fluorophores, TAMRA (5-carboxytetrame thylrhodamine), PBA (1-pyrenebutyric acid), NBD (nitrobenzoxadiazole), OG (Oregon Green), and CF (5-carboxyfluorescein) were conjugated with the dipeptide β-Ala-Lys, the peptide moiety of the well-established peptide transporter substrate β-Ala-Lys(AMCA) (AMCA: 7-amino-
4-methyl-coumarin-3-acetic acid) by modifying it with respect to side-chain
length and functional end groups. The analogs were tested for transport through or inhibition of YdgR, a prototypical peptide transporter from E. coli and apparently homologous to the human PEPT1. Strikingly, none of the dipeptide-fluorophore conjugates nor minor modifications in the reporter substrate were tolerated by YdgR, indicating discrepancies to PEPT1. These findings underscore
intricate substrate recognition mechanisms governing substrate recognition by YdgR.

Original language	English
Article number	e3670
Journal	Journal of Peptide Science
Volume	31
Issue number	3
Number of pages	12
ISSN	1075-2617
DOIs	https://doi.org/10.1002/psc.3670
Publication status	Published - Mar 2025

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@article{c1586cf51d4343f98eda672fe7cf7ea4,

title = "The prototypical oligopeptide transporter YdgR from E. coli exhibits a strict preference for β-Ala-Lys(AMCA)",

abstract = "Fluorescent probes are widely used in cellular imaging and disease diagnosis. Acting as substitute carriers, fluorescent probes can also be used to help transport drugs within cells. In this study, commonly used fluorophores, TAMRA (5-carboxytetrame thylrhodamine), PBA (1-pyrenebutyric acid), NBD (nitrobenzoxadiazole), OG (Oregon Green), and CF (5-carboxyfluorescein) were conjugated with the dipeptide β-Ala-Lys, the peptide moiety of the well-established peptide transporter substrate β-Ala-Lys(AMCA) (AMCA: 7-amino-4-methyl-coumarin-3-acetic acid) by modifying it with respect to side-chainlength and functional end groups. The analogs were tested for transport through or inhibition of YdgR, a prototypical peptide transporter from E. coli and apparently homologous to the human PEPT1. Strikingly, none of the dipeptide-fluorophore conjugates nor minor modifications in the reporter substrate were tolerated by YdgR, indicating discrepancies to PEPT1. These findings underscoreintricate substrate recognition mechanisms governing substrate recognition by YdgR.",

author = "Salvia Sajid and Cecilia Ninh and Ruyu Yan and Maria Raﬁq and Christensen, {Lars Porskj{\ae}r} and J{\o}rgensen, {Mikkel Girke} and Hansen, {Paul Robert} and Henrik Franzyk and Osman Mirza and Prabhala, {Bala Krishna}",

year = "2025",

month = mar,

doi = "10.1002/psc.3670",

language = "English",

volume = "31",

journal = "Journal of Peptide Science",

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publisher = "Wiley",

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T1 - The prototypical oligopeptide transporter YdgR from E. coli exhibits a strict preference for β-Ala-Lys(AMCA)

AU - Sajid, Salvia

AU - Ninh, Cecilia

AU - Yan, Ruyu

AU - Raﬁq, Maria

AU - Christensen, Lars Porskjær

AU - Jørgensen, Mikkel Girke

AU - Hansen, Paul Robert

AU - Franzyk, Henrik

AU - Mirza, Osman

AU - Prabhala, Bala Krishna

PY - 2025/3

Y1 - 2025/3

N2 - Fluorescent probes are widely used in cellular imaging and disease diagnosis. Acting as substitute carriers, fluorescent probes can also be used to help transport drugs within cells. In this study, commonly used fluorophores, TAMRA (5-carboxytetrame thylrhodamine), PBA (1-pyrenebutyric acid), NBD (nitrobenzoxadiazole), OG (Oregon Green), and CF (5-carboxyfluorescein) were conjugated with the dipeptide β-Ala-Lys, the peptide moiety of the well-established peptide transporter substrate β-Ala-Lys(AMCA) (AMCA: 7-amino-4-methyl-coumarin-3-acetic acid) by modifying it with respect to side-chainlength and functional end groups. The analogs were tested for transport through or inhibition of YdgR, a prototypical peptide transporter from E. coli and apparently homologous to the human PEPT1. Strikingly, none of the dipeptide-fluorophore conjugates nor minor modifications in the reporter substrate were tolerated by YdgR, indicating discrepancies to PEPT1. These findings underscoreintricate substrate recognition mechanisms governing substrate recognition by YdgR.

AB - Fluorescent probes are widely used in cellular imaging and disease diagnosis. Acting as substitute carriers, fluorescent probes can also be used to help transport drugs within cells. In this study, commonly used fluorophores, TAMRA (5-carboxytetrame thylrhodamine), PBA (1-pyrenebutyric acid), NBD (nitrobenzoxadiazole), OG (Oregon Green), and CF (5-carboxyfluorescein) were conjugated with the dipeptide β-Ala-Lys, the peptide moiety of the well-established peptide transporter substrate β-Ala-Lys(AMCA) (AMCA: 7-amino-4-methyl-coumarin-3-acetic acid) by modifying it with respect to side-chainlength and functional end groups. The analogs were tested for transport through or inhibition of YdgR, a prototypical peptide transporter from E. coli and apparently homologous to the human PEPT1. Strikingly, none of the dipeptide-fluorophore conjugates nor minor modifications in the reporter substrate were tolerated by YdgR, indicating discrepancies to PEPT1. These findings underscoreintricate substrate recognition mechanisms governing substrate recognition by YdgR.

U2 - 10.1002/psc.3670

DO - 10.1002/psc.3670

M3 - Journal article

SN - 1075-2617

VL - 31

JO - Journal of Peptide Science

JF - Journal of Peptide Science

IS - 3

M1 - e3670

ER -

The prototypical oligopeptide transporter YdgR from E. coli exhibits a strict preference for β-Ala-Lys(AMCA)

Abstract

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