Publications
2014
Lamanna Giuseppe, Grillaud Maxime, Macri Christophe, Chaloin Olivier, Muller Sylviane, Bianco Alberto
Adamantane-based dendrons for trimerization of the therapeutic P140 peptide Article de journal
Dans: Biomaterials, vol. 35, no. 26, p. 7553–7561, 2014, ISSN: 1878-5905.
Résumé | Liens | BibTeX | Étiquettes: Adamantane, Animals, Biotin, C3-symmetry, Dendrimers, Dendrons, Drug Carriers, Female, HSC70 Heat-Shock Proteins, HSPA8 protein, Humans, I2CT, Inbred MRL lpr, Lupus Erythematosus, Mice, P140 peptide, Peptide Fragments, Systemic, Team-Bianco
@article{lamanna_adamantane-based_2014,
title = {Adamantane-based dendrons for trimerization of the therapeutic P140 peptide},
author = {Giuseppe Lamanna and Maxime Grillaud and Christophe Macri and Olivier Chaloin and Sylviane Muller and Alberto Bianco},
doi = {10.1016/j.biomaterials.2014.05.017},
issn = {1878-5905},
year = {2014},
date = {2014-01-01},
journal = {Biomaterials},
volume = {35},
number = {26},
pages = {7553--7561},
abstract = {Dendrons constituted of an adamantane core, a focal point and three arms, were synthetized starting from a multifunctional adamantane derivative. Maleimido groups at the periphery of the scaffold were used to covalently attach the peptide called P140, a therapeutic phosphopeptide controlling disease activity in systemic lupus, both in mice and patients. Biotinylation of the trimers at the focal point was performed using click chemistry and the conjugates were studied in terms of solubility, binding affinity to its receptor, the HSPA8/HSC70 chaperone protein, effect on HSPA8 folding property and in vivo activity. The results showed that the trimerization of P140 peptide does not trigger aggregation or steric hindrances during the interaction with HSPA8 protein. Compared to the monomeric cognate peptide, the trivalent P140 peptide displayed the same capacity, in vitro, to down-regulate HSPA8 activity and, in vivo in MRL/lpr lupus-prone mice, to reduce abnormal blood hypercellularity. The control trimer synthesized with the same scaffold and a scrambled sequence of P140 showed no effect in vivo. This work reveals that adamantane-based scaffolds with a well-defined spatial conformation are promising trivalent systems for molecular recognition and for biomedical applications.},
keywords = {Adamantane, Animals, Biotin, C3-symmetry, Dendrimers, Dendrons, Drug Carriers, Female, HSC70 Heat-Shock Proteins, HSPA8 protein, Humans, I2CT, Inbred MRL lpr, Lupus Erythematosus, Mice, P140 peptide, Peptide Fragments, Systemic, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}
Dendrons constituted of an adamantane core, a focal point and three arms, were synthetized starting from a multifunctional adamantane derivative. Maleimido groups at the periphery of the scaffold were used to covalently attach the peptide called P140, a therapeutic phosphopeptide controlling disease activity in systemic lupus, both in mice and patients. Biotinylation of the trimers at the focal point was performed using click chemistry and the conjugates were studied in terms of solubility, binding affinity to its receptor, the HSPA8/HSC70 chaperone protein, effect on HSPA8 folding property and in vivo activity. The results showed that the trimerization of P140 peptide does not trigger aggregation or steric hindrances during the interaction with HSPA8 protein. Compared to the monomeric cognate peptide, the trivalent P140 peptide displayed the same capacity, in vitro, to down-regulate HSPA8 activity and, in vivo in MRL/lpr lupus-prone mice, to reduce abnormal blood hypercellularity. The control trimer synthesized with the same scaffold and a scrambled sequence of P140 showed no effect in vivo. This work reveals that adamantane-based scaffolds with a well-defined spatial conformation are promising trivalent systems for molecular recognition and for biomedical applications.