Self-assembling peptides and their conjugates offer exceptional potential in nanomedicine. I will present some of our recent work on nanoscale assembled peptides and their conjugates, focussing on lipopeptides and PEG-peptide conjugates. PEGylation is an important technique in the development of conjugates for applications in therapeutics. It is found to greatly influence self-assembly of peptides and proteins-one example from our own work is a peptide which itself forms twisted fibrils but when PEG is attached, self-assembly of the conjugate leads to spherical micelles [1]. The conjugate can be enzymatically degraded using alpha-chymotrypsin, releasing the peptide. This nanocontainer delivery and release system could be useful in therapeutic applications. Thermoresponsive telechelic PEG/peptides with hydrophobic dipeptide end groups (di-tyrosine or di-phenylalanine) were developed, one of which shows a de-gelation transition near body temperature and which may be useful in bioresponsive delivery systems [2]. Examples from our recent work on self-assembling lipopeptides will also be outlined. Our focus is to investigate potential relationships between self-assembly and bioactivity, in particular in the fields of regenerative medicine [3-5], antimicrobial systems [6-7] and immune therapies [8].
Representative Publications
1. Castelletto, V. ; McKendrick, J. M. E. ; Hamley , I. W. ; Cenker, C. ; Olsson, U., Pegylated Amyloid Peptide Nanocontainer Delivery and Release System. Langmuir 2010, 26, 11624-11627.
2. Hamley, I. W. ; Cheng, G. ; Castelletto, V., Self-Assembly of Telechelic Peg End-Capped with Hydrophobic Dipeptides. Macromolecular Bioscience 2011, 11, 1068-1078.
3. Jones, R. R. ; Castelletto, V. ; Connon, C. J. ; Hamley , I. W., Collagen Stimulating Effect of Peptide Amphiphile C16 − Kttks on Human Fibroblasts. Molecular Pharmaceutics 2013, 10, 1063-1069.
4. Gouveia, R. J. ; Castelletto, V. ; Alcock, S. G. ; Hamley , I. W. ; Connon, C. J., Bioactive Films Produced from Self-Assembling Peptide Amphiphiles as Versatile Substrates for Tuning Cell Adhesion and Tissue Architecture in Serum-Free Conditions. J. Mater. Chem. B 2013, 1, 6157-6169.
5. Castelletto, V. ; Gouveia, R. J. ; Connon, C. J. ; Hamley, I. W. ; Seitsonen, J. ; Ruokolainen, J. ; Longo, E. ; Siligardi, G., Influence of Elastase on Alanine-Rich Peptide Hydrogels. Biomater. Sci. 2014, 2, 867-874.
6. Dehsorkhi, A. ; Castelletto, V. ; Hamley, I. W. ; Seitsonen, J. ; Ruokolainen, J., Interaction between a Cationic Surfactant-Like Peptide and Lipid Vesicles and Its Relationship to Antimicrobial Activity. Langmuir 2013, 29, 14246-14253.
7. Hamley , I. W. ; Dehsorkhi, A. ; Castelletto, V., Self-Assembled Arginine-Coated Peptide Nanosheets in Water. Chem. Comm. 2013, 49, 1850-1852.
8. Hamley, I. W. ; Kirkham, S. ; Dehsorkhi, A. ; Castelletto, V. ; Reza, M. ; Ruokolainen, J., Toll-Like Receptor Agonist Lipopeptides Self-Assemble into Distinct Nanostructures. Chem. Comm. 2014, 50, 15948-15951.
Contact : diego.pontoni@esrf.fr
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