resumo
Self-assembled peptide-based hydrogels are archetypical nanostructured materials with a plethora of foreseeable applications in nanomedicine and as biomaterials. N-protected di- and tri-peptides are effective minimalist (molecular) hydrogelators. Independent variation of the capping group, peptide sequence and side chain modifications allows a wide chemical space to be explored and hydrogel properties to be tuned. In this work, we report the synthesis of a focused library of dehydrodipeptides N-protected with 1-naphthoyl and 2-naphthylacetyl groups. The 2-naphthylacetyl group was extensively reported for preparation of peptide-based self-assembled hydrogels, whereas the 1-naphthaloyl group was largely overlooked, owing presumably to the lack of a methylene linker between the naphthalene aromatic ring and the peptide backbone. Interestingly, dehydrodipeptides N-capped with the 1-naphthyl moiety afford stronger gels, at lower concentrations, than the 2-naphthylacetyl-capped dehydrodipeptides. Fluorescence and circular dichroism spectroscopy showed that the self-assembly of the dehydrodipeptides is driven by intermolecular aromatic & pi;-& pi; stacking interactions. Molecular dynamics simulations revealed that the 1-naphthoyl group allows higher order aromatic & pi;-& pi; stacking of the peptide molecules than the 2-naphthylacetyl group, together with hydrogen bonding of the peptide scaffold. The nanostructure of the gel networks was studied by TEM and STEM microscopy and was found to correlate well with the elasticity of the gels. This study contributes to understanding the interplay between peptide and capping group structure on the formation of self-assembled low-molecular-weight peptide hydrogels. Moreover, the results presented here add the 1-naphthoyl group to the palette of capping groups available for the preparation of efficacious low-molecular-weight peptide-based hydrogels.
palavras-chave
LINEAR CONSTRAINT SOLVER; SUPRAMOLECULAR HYDROGELS; WATER MODELS; GELS; CHIRALITY; LINCS
categoria
Polymer Science
autores
Vilaça, H; Carvalho, A; Castro, T; Castanheira, EMS; Hilliou, L; Hamley, I; Melle-Franco, M; Ferreira, PMT; Martins, JA
nossos autores
Manuel Melle-Franco
Investigador Principalagradecimentos
This work was funded by National Funds through FCT-Portuguese Foundation for Science and Technology under the Project PTDC/QUI-QOR/29015/2017, CQ/UM UID/QUI/00686/2013 and UID/QUI/0686/2016, UID/CTM/50025/2019 and CF-UM-UP (UIDB/04650/2020). The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project No 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC).