Peptide Targeting of an Intracellular Receptor of the Secretory Pathway

Biochemistry
Alina Tirla, Pablo Rivera-Fuentes

Abstract

Numerous peptides serve as natural ligands of intra- and extracellular receptors. The presence of charged amino acids, however, often hinders the membrane-crossing ability of some of these peptides and renders them unsuitable as chemical probes for perturbing or imaging intracellular targets. In this report, we show that addition of a few natural and unnatural amino acids enhances the cellular uptake and intracellular localization of a highly charged Lys-Asp-Glu-Leu (KDEL) peptide to target the corresponding receptor of the secretory pathway. Live-cell imaging experiments revealed that, through interaction with the KDEL receptor, the peptide is delivered to the endoplasmic reticulum (ER), where it accumulates preferentially. The enhanced uptake and selectivity of this peptide make it a good probe for monitoring disruptions in retrograde transport and ER stress in living cells without any genetic modifications.

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Citations

Jun 7, 2019·Angewandte Chemie·Yangyang ChengStefan Matile
Oct 12, 2019·Chembiochem : a European Journal of Chemical Biology·Quentin LaurentStefan Matile
Jan 4, 2020·Angewandte Chemie·Zacharias ThielPablo Rivera-Fuentes
Nov 13, 2019·Current Cancer Drug Targets·Chu Xin Ng, Sau Har Lee
Sep 26, 2020·Chembiochem : a European Journal of Chemical Biology·Rémi MartinentStefan Matile
Jun 25, 2021·Chemical Science·Yangyang ChengStefan Matile
Jul 27, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Ange B IlangalaGéraldine Piel
Sep 2, 2021·JACS Au·Quentin LaurentStefan Matile

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