New self-assembled supramolecular hydrogels based on dehydropeptides

Supramolecular hydrogels rely on small molecules that self-assemble in water as a result of the cooperative effect of several relatively weak intermolecular interactions. Peptide-based low molecular weight hydrogelators have attracted enormous interest owing to the simplicity of small molecules combined with the versatility and biocompatibility of peptides. In this work, naproxen, a well known non-steroidal anti-inflammatory drug, was N-conjugated with various dehydrodipeptides to give aromatic peptide amphiphiles that resist proteolysis. Molecular dynamics simulations were used to obtain insight into the underlying molecular mechanism of self-assembly and to rationalize the design of this type of hydrogelators. The results obtained were in excellent agreement with the experimental observations. Only dehydrodipeptides having at least one aromatic amino acid gave hydrogels. The characterization of the hydrogels was carried out using transmission electron microscopy (TEM), circular dichroism (CD), fluorescence spectroscopy and also rheological assays.

Thanks are due to Foundation for Science and Technology (FCT) – Portugal, QREN and program FEDER/COMPETE for financial support through Centre of Chemistry (CQ-UM) of University of Minho. FCT is also acknowledged for PhD grants of G. Pereira (SFRH/BD/38766/2007), H. Vilaça (SFRH/BD/72651/2010) and T. G. Castro (SFRH/BD/79195/2011), co-funded by the European Social Fund. The NMR spectrometer Bruker Avance III 400 is part of the Portuguese NMR Network (Rede/1517/RMN/2005) which is also supported by the FCT.