Titre :

Binding of Gold(III) Porphyrin by the Pro-metastatic Regulatory Protein Human Galectin-3

Auteur(s) :

Bogoeva, Vanya [Auteur]
Rangelov, Miroslav [Auteur]
Todorova, Nadezhda [Auteur]
Lambert, Annie [Auteur]
Bridot, Clarisse [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Yordanova, Anna [Auteur]
Roos, Goedele [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Grandjean, Cyrille [Auteur]
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]

Titre de la revue :

Molecules

Nom court de la revue :

Molecules

Numéro :

24

Pagination :

4561

Éditeur :

MDPI AG

Date de publication :

2019-12-12

ISSN :

1420-3049

Mot(s)-clé(s) en anglais :

gold porphyrin
galectin‐3
cytotoxicity
tumor associated carbohydrate antigen
affinity
microscale thermophoresis
tryptophan fluorescence
isothermal titration calorimetry
molecular dynamics relaxation
molecular docking

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

Gold(III) porphyrin presents an attractive alternative to the use of, for example, cisplatin in chemotherapy. However, approaches that allow to selectively target cancer cells are highly sought. Many plant and mammalian ...
Lire la suite >Gold(III) porphyrin presents an attractive alternative to the use of, for example, cisplatin in chemotherapy. However, approaches that allow to selectively target cancer cells are highly sought. Many plant and mammalian lectins have been shown to bind oligosaccharide sequences of the aberrant glycosylation pattern found on cancerous tumors. For example human galectin-3, of the galectin family specific for β-galactoside, is overexpressed in the extracellular matrix of tumorigenous and metastatic tissues. We searched for non-carbohydrate ligands for galectin-3 that can guide a cytotoxic drug to the cancer cells by maintaining its affinity for tumor associated carbohydrate antigens. Previous findings showed that zinc tetrasulfonatophenylporphyrin can bind galectin-3 with sub-micromolar affinity without disturbing lactose binding. Gold(III) porphyrin is not only cytotoxic to cancer cells, it knows also a potential application as photosensitiser in photodynamic therapy. We investigated the binding of gold(III) porphyrin to galectin-3 using different biophysical interaction techniques and demonstrated a low micromolar affinity of human galectin-3 for the cytotoxic compound. Co-crystallization attempts in order to understand the binding mode of gold porphyrin to galectin-3 failed, but molecular docking emphasized a highly populated secondary binding site that does not hinder lactose or Thomsen Friendenreich disaccharide binding. This suggests that gold(III) porphyrin might significantly enhance its concentration and delivery to cancer cells by binding to human galectin-3 that keeps its orientation towards tumor associated carbohydrate antigens.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Autre(s) projet(s) ou source(s) de financement :

RILA program of the Hubert Curien foundation, project code 38675 VG

Établissement(s) :

Université de Lille
CNRS

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Computational Molecular Systems Biology

Date de dépôt :

2020-11-10T06:01:26Z
2020-11-16T16:33:07Z
2021-01-07T09:52:03Z