Becker, Bastian ; Englert, Simon ; Schneider, Hendrik ; Yanakieva, Desislava ; Hofmann, Sarah ; Dombrowsky, Carolin ; Macarrón Palacios, Arturo ; Bitsch, Sebastian ; Elter, Adrian ; Meckel, Tobias ; Kugler, Benedikt ; Schirmacher, Anastasyia ; Avrutina, Olga ; Diederichsen, Ulf ; Kolmar, Harald (2024)
Multivalent dextran hybrids for efficient cytosolic delivery of biomolecular cargoes.
In: Journal of Peptide Science : the official Journal of the European Peptide Society, 2021, 27 (4)
doi: 10.26083/tuprints-00017809
Artikel, Zweitveröffentlichung, Verlagsversion
 | Es ist eine neuere Version dieses Eintrags verfügbar. |
Kurzbeschreibung (Abstract)
The development of novel biotherapeutics based on peptides and proteins is often limited to extracellular targets, because these molecules are not able to reach the cytosol. In recent years, several approaches were proposed to overcome this limitation. A plethora of cell‐penetrating peptides (CPPs) was developed for cytoplasmic delivery of cell‐impermeable cargo molecules. For many CPPs, multimerization or multicopy arrangement on a scaffold resulted in improved delivery but also higher cytotoxicity. Recently, we introduced dextran as multivalent, hydrophilic polysaccharide scaffold for multimerization of cell‐targeting cargoes. Here, we investigated covalent conjugation of a CPP to dextran in multiple copies and assessed the ability of resulted molecular hybrid to enter the cytoplasm of mammalian cells without largely compromising cell viability. As a CPP, we used a novel, low‐toxic cationic amphiphilic peptide L17E derived from M‐lycotoxin. Here, we show that cell‐penetrating properties of L17E are retained upon multivalent covalent linkage to dextran. Dextran‐L17E efficiently mediated cytoplasmic translocation of an attached functional peptide and a peptide nucleic acid (PNA). Moreover, a synthetic route was established to mask the lysine side chains of L17E with a photolabile protecting group thus opening avenues for light‐triggered activation of cellular uptake.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | Becker, Bastian ; Englert, Simon ; Schneider, Hendrik ; Yanakieva, Desislava ; Hofmann, Sarah ; Dombrowsky, Carolin ; Macarrón Palacios, Arturo ; Bitsch, Sebastian ; Elter, Adrian ; Meckel, Tobias ; Kugler, Benedikt ; Schirmacher, Anastasyia ; Avrutina, Olga ; Diederichsen, Ulf ; Kolmar, Harald |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Multivalent dextran hybrids for efficient cytosolic delivery of biomolecular cargoes |
| Sprache: | Englisch |
| Publikationsjahr: | 12 Februar 2024 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 2021 |
| Ort der Erstveröffentlichung: | New York |
| Verlag: | John Wiley & Sons |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Journal of Peptide Science : the official Journal of the European Peptide Society |
| Jahrgang/Volume einer Zeitschrift: | 27 |
| (Heft-)Nummer: | 4 |
| Kollation: | 18 Seiten |
| DOI: | 10.26083/tuprints-00017809 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/17809 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (Abstract): | The development of novel biotherapeutics based on peptides and proteins is often limited to extracellular targets, because these molecules are not able to reach the cytosol. In recent years, several approaches were proposed to overcome this limitation. A plethora of cell‐penetrating peptides (CPPs) was developed for cytoplasmic delivery of cell‐impermeable cargo molecules. For many CPPs, multimerization or multicopy arrangement on a scaffold resulted in improved delivery but also higher cytotoxicity. Recently, we introduced dextran as multivalent, hydrophilic polysaccharide scaffold for multimerization of cell‐targeting cargoes. Here, we investigated covalent conjugation of a CPP to dextran in multiple copies and assessed the ability of resulted molecular hybrid to enter the cytoplasm of mammalian cells without largely compromising cell viability. As a CPP, we used a novel, low‐toxic cationic amphiphilic peptide L17E derived from M‐lycotoxin. Here, we show that cell‐penetrating properties of L17E are retained upon multivalent covalent linkage to dextran. Dextran‐L17E efficiently mediated cytoplasmic translocation of an attached functional peptide and a peptide nucleic acid (PNA). Moreover, a synthetic route was established to mask the lysine side chains of L17E with a photolabile protecting group thus opening avenues for light‐triggered activation of cellular uptake. |
| Freie Schlagworte: | cell penetrating peptide, intracellular delivery, multimerization, oligosaccharides, peptide nucleic acids, peptides |
| ID-Nummer: | Artikel-ID: e3298 |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-178094 |
| Zusätzliche Informationen: | This article also appears in: SPP 1623 - Chemoselective reactions for the synthesis and application of functional proteins |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 540 Chemie 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie |
| Fachbereich(e)/-gebiet(e): | 07 Fachbereich Chemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut |
| Hinterlegungsdatum: | 12 Feb 2024 13:50 |
| Letzte Änderung: | 13 Feb 2024 07:50 |
| PPN: | |
| Export: | |
| Suche nach Titel in: | TUfind oder in Google |
Verfügbare Versionen dieses Eintrags
- Multivalent dextran hybrids for efficient cytosolic delivery of biomolecular cargoes. (deposited 12 Feb 2024 13:50) [Gegenwärtig angezeigt]
 |
Frage zum Eintrag |
Optionen (nur für Redakteure)
 |
Redaktionelle Details anzeigen |
Drucken
Impressum