dc.contributor.author
Balamurugan, Kanagasabai
dc.contributor.author
Koehler, Linda
dc.contributor.author
Dürig, Jan-Niklas
dc.contributor.author
Hempel, Ute
dc.contributor.author
Rademann, Jörg
dc.contributor.author
Hintze, Vera
dc.contributor.author
Pisabarro, M. Teresa
dc.date.accessioned
2021-12-03T08:34:14Z
dc.date.available
2021-12-03T08:34:14Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/32983
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-32709
dc.description.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.
en
dc.format.extent
12 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
angiogenesis
en
dc.subject
extracellular matrix (ECM)
en
dc.subject
glycosaminoglycans (GAG)
en
dc.subject
hyaluronan (HA)
en
dc.subject
platelet derived growth factor (PDGF)
en
dc.subject
vascular endothelial growth factor (VEGF)
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::570 Biowissenschaften; Biologie
dc.title
Structural insights into the modulation of PDGF/PDGFR-β complexation by hyaluronan derivatives
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1515/hsz-2021-0173
dcterms.bibliographicCitation.journaltitle
Biological Chemistry
dcterms.bibliographicCitation.number
11
dcterms.bibliographicCitation.pagestart
1441
dcterms.bibliographicCitation.pageend
1452
dcterms.bibliographicCitation.volume
402
dcterms.bibliographicCitation.url
https://doi.org/10.1515/hsz-2021-0173
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Pharmazie
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refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
1437-4315
refubium.resourceType.provider
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