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Mixed alpha/beta-Peptides as a Class of Short Amphipathic Peptide Hydrogelators with Enhanced Proteolytic Stability

Mangelschots J., Bibian M., Gardiner J., Waddington L., Van Wanseele Y., Van Eeckhaut A., Diaz Acevedo MM., Van Mele B., Madder A., Hoogenboom R. and Ballet S.Mixed alpha/beta-Peptides as a Class of Short Amphipathic Peptide Hydrogelators with Enhanced Proteolytic Stability,Biomacromolecules,17(2): 437-445,2016 (FEB).

doi: 10.1021/acs.biomac.5b01319

Peptide hydrogels are a highly promising class of materials for biomedical application, albeit facing many challenges with regard to stability and tunability. Here, we report a new class of amphipathic peptide hydrogelators, namely mixed alpha/beta-peptide hydrogelators. These mixed alpha/beta-gelators possess good rheological properties (high storage moduli) and form transparent self-supporting gels with shear-thinning behavior. Infrared spectroscopy indicates the presence of beta-sheets as the underlying secondary structure. Interestingly, self-assembled nanofibers of the mixed alpha/beta-peptides display unique structural morphologies with alteration of the C-terminus (acid vs amide) playing a key role in the fiber formation and gelation properties of the resulting hydrogels. The incorporation of beta 3-homoamino acid residues within the mixed alpha/beta-peptide gelators led to an increase in proteolytic stability of the peptides under nongelating conditions (in solution) as well as gelating conditions (as hydrogel). Under diluted conditions, degradation of mixed alpha/beta-peptides in the presence of elastase was slowed down 120-fold compared to that of an alpha-peptide, thereby demonstrating beneficial enzymatic resistance for hydrogel applications in vivo. In addition, increased half-life values were obtained for the mixed alpha/beta-peptides in human blood plasma, as compared to corresponding alpha-peptides. It was also found that the mixed alpha/beta-peptides were amenable to injection via needles used for subcutaneous administrations. The preformed peptide gels could be sheared upon injection and were found to quickly reform to a state close to that of the original hydrogel. The shown properties of enhanced proteolytic stability and injectability hold great promise for the use of these novel mixed alpha/beta-peptide hydrogels for applications in the areas of tissue engineering and drug delivery.

BibTeX

@article{,
    author  = "Mangelschots, J. ; Bibian, M.  ; Gardiner, J. ; Waddington, L. ; Van Wanseele, Y. ; Van Eeckhaut, A. ; Diaz Acevedo, MM. ; Van Mele, B. ; Madder, A. ; Hoogenboom, R. ; Ballet, S.",
    title   = "Mixed alpha/beta-Peptides as a Class of Short Amphipathic Peptide Hydrogelators with Enhanced Proteolytic Stability",
    journal = "Biomacromolecules",
    year    = "2016",
    volume  = "17",
    number  = "2",
    pages   = "437-445",
    month   = "FEB",
    doi     = "10.1021/acs.biomac.5b01319",
    note    = "",
}