Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/90813
Title: Hierarchical design of hyaluronic acid-peptide constructs for glioblastoma targeting: Combining insights from NMR and molecular dynamics simulations
Authors: 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: 2020
Publisher: Elsevier
Project: POCI-01-0145-FEDER- 016648 
PEst- UID/NEU/04539/2013 
POCI-01-0145-FEDER-007440 
UID/QUI/00313/2020 
IF/00286/2015 
UID/BIM/04501/2019 
POCI-01-0145-FEDER-007628 
UID/IC/00051/2019 
SFRH/BD/133996/2017 
SFRH/BD/149138/2019 
Serial title, monograph or event: Journal of Molecular Liquids
Volume: 315
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.
URI: https://hdl.handle.net/10316/90813
ISSN: 01677322
DOI: 10.1016/j.molliq.2020.113774
Rights: openAccess
Appears in Collections:I&D CQC - Artigos em Revistas Internacionais

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