BioAdhePepGel

Self-assembled minimalist peptide hydrogels inspired by mussel adhesive proteins for biomedical applications

The properties that marine mussel adhesive proteins display have attracted considerable attention due to their ability to form strong interactions with various substances in water environments. These proteins are characterized by the presence of 3,4-dihydroxy-L-phenylalanine. The catechol moiety is believed to be involved in the interfacial binding and in the solidification of the adhesive proteins. Catechol is known to bind to organic and inorganic surfaces through the formation of reversible non-covalent interactions such as hydrogen bonds, pi-pi electron interactions or ionic interactions. This project aims to develop new adhesive low molecular weight peptide hydrogels based on catechol amino acid derivatives. These nanostructured materials will be tested for biocompatibility and bioactivity and evaluated as drug delivery systems and in the development of medical textiles. The challenge placed by the catechol moiety in the synthesis of these small peptide hydrogelators will be overcome by applying new strategies that involve well known synthetic procedures such as Michael additions, substitution reactions, Suzuki-Miyaura cross-couplings and the Ugi reaction. The new compounds that will be prepared include small dehydropeptides N-protected with catechol derivatives and peptides with ?-substituted catechol amino acids. The self-assembly capability of the catechol based peptide hydrogelators will be evaluated together with the in vitro stability of the bydrogels. The viscoelastic behavior of these materials will be determined by measuring the rheological properties. The adhesive forces of the catechol hydrogels will be measured using atomic force microscopy with several types of probes. The hydrogels with the adequate characteristics for biomedical applications will be submitted to biocompatibility assays in vitro and in vivo together with bacterial viability tests and anti-inflammatory activity assays. The catechol peptide nanostructured materials with the best characteristics will be evaluated as drug delivery nanocarriers and in the fabrication of adhesive textiles for wound dressing. Although there are several reports in the literature concerning catechol polymeric hydrogels, there are very few about self-assembled peptide hydrogelators. The innovation of this project relies on the preparation and characterization of short peptide hydrogelators based on new catecholic amino acids and in testing their application as drug delivery systems and for medical textiles. This proposal is supported by the expertise of a multidisciplinary research team with competencies in the synthesis of amino acid derivatives, in the preparation and characterization of hydrogels, in biological assays and in drug delivery systems and medical textiles. Also, the already established collaborations with other national and international research centers will continue and new ones will be developed.

Universidade do Minho (UM)
Paula M. T. Ferreira, PI (CQUM)
José A. Martins, Co-PI (CQUM)
Luís S. Monteiro, (CQUM)
Maria J. R. P. Queiroz, (CQUM)
Peter Jervis (CQUM)
Elisabete M. Castanheira, (CFUM)
Rui da Cunha Pereira, (CFUM)
Loic Hillou – Instituto de Polímeros e Compósitos
Graça Maria Soares – Centro de Ciência e Tecnologia Têxtil
Jorge Santos – Centro de Ciência e Tecnologia Têxtil
Teresa F. Ramos – Centro de Ciência e Tecnologia Têxtil

REQUIMTE – Rede de Química e Tecnologia – Associação (REQUIMTE-P) – Laboratório Associado para a Química Verde – Tecnologias e Processos Limpos (Norte)
Fátima Paiva-Martins
Paula B. Andrade
Patrícia Valentão
David M. Pereira