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http://hdl.handle.net/10773/37254
Title: | Hierarchical design of hyaluronic acid-peptide constructs for glioblastoma targeting: combining insights from NMR and molecular dynamics simulations |
Author: | Mendes, Maria Cova, Tânia Basso, João Ramos, M. Luísa Vitorino, Rui Sousa, João Pais, Alberto Vitorino, Carla |
Keywords: | Hyaluronic acid C(RGDfK H7k(R2)2 Polymer-peptide conjugates Glioblastoma |
Issue Date: | 1-Oct-2020 |
Publisher: | Elsevier |
Abstract: | The main bottleneck of glioblastoma still relies on the existence of the blood brain-blood brain tumor dual barrier, along with the lack of therapy specificity. The present work deals with the question of whether (and how) different targeting hyaluronic acid (HA)-peptide [c(RGDfK) and/or H7K(R2)2] moieties hierarchically interact with each other, to ensure a unique entity with specificity to glioblastoma. A dual experimental-computational approach, encompassing nuclear magnetic resonance and molecular dynamics simulations is enclosed. Relevant contact patterns based on the identification of the stabilizing/destabilizing noncovalent interactions within the constructs are detailed. The synthesis pathway requires the HA-c(RGDfK)-H7k(R2)2 association hierarchy, stemming from the size and amino acid residue rearrangement, in the 1:1 M ratio, to obtain a stable conjugate ultimately able to interact with the tumor cell membrane. To our knowledge, the structural and mechanistic rationale for the formation of hybrid polymer-peptide constructs, including HA-c(RGDfK)-H7k(R2)2, for glioblastoma has not been addressed so far. |
Peer review: | yes |
URI: | http://hdl.handle.net/10773/37254 |
DOI: | 10.1016/j.molliq.2020.113774 |
ISSN: | 0167-7322 |
Appears in Collections: | IBIMED - Artigos DCM - Artigos |
Files in This Item:
File | Description | Size | Format | |
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Hierarchical design of hyaluronic acid-peptide constructs for.pdf | 3.03 MB | Adobe PDF | View/Open |
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