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Montcada i Reixac, Spain

Pulido D.,Combinatorial Chemistry Unit | Pulido D.,CIBER ISCIII | Albericio F.,CIBER ISCIII | Albericio F.,Barcelona Institute for Research in Biomedicine | And 3 more authors.
Organic Letters

A highly versatile synthetic strategy is described to generate multimodal and multivalent platforms based on a diethylenetriaminepentaacetic (DTPA) core. Compounds with different functionalization patterns, from mono- to pentamodal, have been prepared using robust and simple chemistry. © 2014 American Chemical Society. Source

Roses C.,University of Girona | Carbajo D.,Combinatorial Chemistry Unit | Carbajo D.,CIBER ISCIII | Sanclimens G.,Combinatorial Chemistry Unit | And 13 more authors.

In this study, we combined a cell-penetrating γ-peptide, PEG-1, with antimicrobial undecapeptides in order to provide compounds with anticancer properties against MDA-MB-231 human breast cancer cells. We demonstrated that the conjugates were more cytotoxic than Ac-PEG-1 and the parent undecapeptides. We also evaluated the toxicity of the conjugates against non-malignant cells. The peptide conjugate with the best biological profile was BP77-PEG-1, which, at 10 μM, showed a 71% growth inhibition in MDA-MB-231 cells and only a 17% inhibition in non-malignant cells. Therefore, this study suggests that PEG-1 mediated the undecapeptide delivery into cancer cells and that these conjugates are the proof-of-concept of this strategy to generate improved anticancer drugs based on peptides. © 2011 Elsevier Ltd. All rights reserved. Source

Seelbach R.J.,AO Research Institute Davos | Seelbach R.J.,University of Barcelona | Fransen P.,Barcelona Institute for Research in Biomedicine | Fransen P.,CIBER ISCIII | And 16 more authors.
Acta Biomaterialia

The controlled presentation of biofunctionality is of key importance for hydrogel applications in cell-based regenerative medicine. Here, a versatile approach was demonstrated to present clustered binding epitopes in an injectable, thermoresponsive hydrogel. Well-defined multivalent dendrimers bearing four integrin binding sequences and an azido moiety were covalently grafted to propargylamine-derived hyaluronic acid (Hyal-pa) using copper-catalyzed alkyne-azide cycloaddition (CuAAC), and then combined with pN-modified hyaluronan (Hyal-pN). The dendrimers were prepared by synthesizing a bifunctional diethylenetriamine pentaacetic acid core with azido and NHBoc oligo(ethylene glycol) aminoethyl branches, then further conjugated with solid-phase synthesized RGDS and DGRS peptides. Azido terminated pN was synthesized by reversible addition-fragmentation chain transfer polymerization and reacted to Hyal-pa via CuAAC. Nuclear magnetic resonance (NMR), high performance liquid chromatography, size exclusion chromatography and mass spectroscopy proved that the dendrimers had well-defined size and were disubstituted. NMR and atomic absorption analysis confirmed the hyaluronan was affixed with dendrimers or pN. Rheological measurements demonstrated that dendrimers do not influence the elastic or viscous moduli of thermoresponsive hyaluronan compositions at a relevant biological concentration. Finally, human mesenchymal stromal cells were encapsulated in the biomaterial and cultured for 21 days, demonstrating the faculty of this dendrimer-modified hydrogel as a molecular toolbox for tailoring the biofunctionality of thermoresponsive hyaluronan carriers for biomedical applications. © 2014 Acta Materialia Inc. Source

Seelbach R.J.,AO Research Institute Davos | Fransen P.,Barcelona Institute for Research in Biomedicine | Pulido D.,University of Barcelona | Pulido D.,Biomedical Research Networking Center in Bioengineering | And 11 more authors.
Macromolecular Bioscience

BMP-2 and TGF-β1 released from injectable thermoresponsive hydrogels are studied in the presence and absence of branched macromolecules bearing BMP-2 or TGF-β1 affinity binding peptides. The synthesized branched macromolecules and the gelling compositions before and after loading with either BMP-2 or TGF-β1 are characterized physico-chemically and show a significantly lower amount of proteins released in the presence of the affinity binding peptide macromolecules. This study illustrates the potential of affinity binding peptide functionalized dendrimers to modulate the local delivery and availability of growth factors important for musculoskeletal regeneration therapies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Sanchez-Nieves J.,University of Alcala | Sanchez-Nieves J.,CIBER ISCIII | Fransen P.,Barcelona Institute for Research in Biomedicine | Pulido D.,CIBER ISCIII | And 13 more authors.
European Journal of Medicinal Chemistry

Here we synthesized carbosilane, generation 1 to 3, and PEG-based dendrons functionalized at the periphery with NHBoc groups and at the focal point with azide and alkyne moieties, respectively. The coupling of these two types of dendrons via click chemistry led to the formation of new hybrid dendrimers with two distinct moieties, the hydrophobic carbosilane and the hydrophilic PEG-based dendron. The protected dendrimers were transformed into cationic ammonium dendrimers. These unique amphiphilic dendrimers were studied as vectors for gene therapy against HIV in peripheral blood mononuclear cells (PBMC) and their performance was compared with that of a PEG-free carbosilane dendrimer. The presence of the PEG moiety afforded lower toxicities and evidenced a weaker interaction between dendrimers and siRNA when compared to the homodendrimer analogous. Both features, lower toxicity and lower dendriplex strength, are key properties for use of these vectors as carriers of nucleic material. © 2014 Elsevier B.V. All rights reserved. Source

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