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Stillger, Katharina ORCID: 0000-0001-5811-6389, Platz‐Baudin, Eric ORCID: 0009-0000-9727-0936, Friedland, Florian, Ruppel, Melina, Sticker, Coco‐Louisa, Bodenhausen, Anne, Noetzel, Erik ORCID: 0000-0003-3163-6848 and Neundorf, Ines ORCID: 0000-0001-6450-3991 (2025). First Steps toward the Design of Peptides that Influence the Intracellular Palmitoylation Machinery. ChemBioChem, 26 (10). pp. 1-13. Wiley. ISSN 1439-4227

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Abstract

[Artikel-Nr.: e202500218] Protein S‐palmitoylation is a reversible posttranslational modification transferring the 16‐carbon fatty acid palmitate to cysteines. It plays a critical role in many cellular processes by influencing protein function, localization, stability, and protein–protein interactions and has a significant impact on various physiological and pathological conditions. This emphasizes the need to develop new technologies to study and treat diseases associated with aberrant palmitoylation. To address these challenges, cell‐permeable peptides containing an Asp–His–His–Cys (DHHC) palmitoylation motif are presented aiming to affect intracellular protein S‐palmitoylation. A small library of peptides is generated and screened for cellular uptake and cell compatibility. Interestingly, the newly designed peptides internalize to high extent into different cell lines and human breast cell spheroids dependent on their palmitoylation motif. In addition, out of this screen, DC‐2 is identified as very potent and this peptide is investigated in more detail concerning its impact on palmitoylated proteins that are connected to cancer progression. These initial explorations highlight that DC‐2 affected the localization of HRas and altered S‐palmitoylation‐related signaling cascades of epidermal growth factor receptor. These findings suggest a peptide‐driven impact on proteins having palmitoylation sites and highlight cell‐permeable DHHC peptides as a potential tool to be further evolved in the context of palmitoylation and cancer.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Stillger, Katharina UNSPECIFIED https://orcid.org/0000-0001-5811-6389 UNSPECIFIED Platz‐Baudin, Eric UNSPECIFIED https://orcid.org/0009-0000-9727-0936 UNSPECIFIED Friedland, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruppel, Melina UNSPECIFIED UNSPECIFIED UNSPECIFIED Sticker, Coco‐Louisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Bodenhausen, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Noetzel, Erik UNSPECIFIED https://orcid.org/0000-0003-3163-6848 UNSPECIFIED Neundorf, Ines UNSPECIFIED https://orcid.org/0000-0001-6450-3991 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-802727
Identification Number:	10.1002/cbic.202500218
Journal or Publication Title:	ChemBioChem
Volume:	26
Number:	10
Page Range:	pp. 1-13
Number of Pages:	13
Date:	27 May 2025
Publisher:	Wiley
ISSN:	1439-4227
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences External institution
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry Außeruniversitäre Forschungseinrichtungen > Forschungszentrum Jülich
Subjects:	Chemistry and allied sciences Life sciences
Uncontrolled Keywords:	Keywords Language cysteine palmitoylations ; epidermal growth factor receptors ; peptides ; protein modifications ; ZDHHC enzymes English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/80272