Structural insights into the modulation of PDGF/PDGFR-β complexation by hyaluronan derivatives

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

Angiogenesis is an important physiological process playing a crucial role in wound healing and cancer progression. Vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) are key players in angiogenesis. Based on previous findings regarding the modulation of VEGF activity by glycosaminoglycans (GAG), here we explore the interaction of hyaluronan (HA)-based GAG with PDGF and its receptor PDGFR-β by applying molecular modeling and dynamics simulations in combination with surface plasmon resonance (SPR). Computational analysis on the interaction of oligo-hyaluronan derivatives with different sulfation pattern and functionalization shows that these GAG interact with PDGF in relevant regions for receptor recognition, and that high sulfation as well as modification with the TAMRA group convey stronger binding. On the other hand, the studied oligo-hyaluronan derivatives are predicted to scarcely recognize PDGFR-β. SPR results are in line with the computational predictions regarding the binding pattern of HA tetrasaccharide (HA4) derivatives to PDGF and PDGFR-β. Furthermore, our experimental results also show that the complexation of PDGF to PDGFR-β can be modulated by HA4 derivatives. The results found open the path for considering HA4 derivatives as potential candidates to be exploited for modulation of the PDGF/PDGFR-β signaling system in angiogenesis and related disease conditions.

Details

OriginalspracheEnglisch
Seiten (von - bis)1441-1452
Seitenumfang12
Fachzeitschrift Biological chemistry
Jahrgang402
Ausgabenummer11
PublikationsstatusVeröffentlicht - 26 Okt. 2021
Peer-Review-StatusJa

Externe IDs

Scopus 85111567099
ORCID /0000-0002-5611-9903/work/142244032

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • Carbohydrate Conformation, Humans, Hyaluronic Acid/chemistry, Models, Molecular, Platelet-Derived Growth Factor/chemistry, Receptor, Platelet-Derived Growth Factor beta/chemistry, Recombinant Proteins/chemistry, Surface Plasmon Resonance

Bibliotheksschlagworte