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Polypeptide synthesis

A number of fundamental investigations from the group on the polymerisation of amino acid NCAs were carried out in the past. This includes investigation of NCA polymerisation conditions, copolymerisation characteristics as well as the first light induced NCA polymerisation, among others. 

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GPC traces of light induced NCA polymerisation


NCA terpolymerisation diagram

Selected publications:

  • Habraken, G.J.M., Peeters, M., Dietz, C.H.J.T., Koning, C.E., Heise, A. How controlled and versatile is N-carboxy anhydride (NCA) polymerization at 0 °C? Effect of temperature on homo-, block- and graft (co)polymerization. Polym. Chem. 2010, 1, 514. 

  • Zelzer, M., Heise, A. Determination of copolymerisation characteristics in the N-carboxy anhydride polymerisation of two amino acids. Polym. Chem. 2013, 4, 3896. 

  • Stukenkemper, T., Jansen, J.F.G.A., Lavilla, C., Dias, A.A., Brougham, D.F., Heise, A. Polypeptides by light: Photo-polymerization of N -carboxyanhydrides (NCA). Polym. Chem. 2017, 8, 828.

  • Lavilla, C., Byrne, M., Heise, A. Block-Sequence-Specific Polypeptides from α-Amino Acid N-Carboxyanhydrides: Synthesis and Influence on Polypeptide Properties. Macromolecules 2016, 49, 2942. 

  • Lavilla, C., Yilmaz, G., Uzunova, V., Napier, R., Becer, C.R., Heise, A. Block-Sequence-Specific Glycopolypeptides with Selective Lectin Binding Properties. Biomacromolecules 2017, 18 (6), pp. 1928.

  • Huang, J., Heise, A. Stimuli responsive synthetic polypeptides derived from N-carboxyanhydride (NCA) polymerisation. Chem. Soc. Rev. 2013, 42, 7373.

Polypeptide nanoparticles

Functional nanoparticles play a prominent role in nanomedicine as diagnostics as well as for active therapeutic delivery. The Heise group has developed and investigated self-assembly methodologies towards micelle and polymersomes as well as solid particles. In particular, a new mini emulsion precess for the NCA polymerisation in an aqueous environment was developed for the scalable production of surface functional nanoparticles. A special interest is in the development of glycosylated nanoparticles due to the prominent role of glycans in biological processes such as infection, cell communication, etc.  

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anisotropic versus spherical block copolypeptide particles through solvent choice 

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polypeptide particles obtained from miniemulsion polymerisation

Selected publications:

  • Huang, J., Bonduelle, C., Thévenot, J., Lecommandoux, S., Heise, A. Biologically active polymersomes from amphiphilic glycopeptides. J. Am. Chem. Soc. 2012, 134, 119. 

  • Bobbi, E., Sabagh, B., Cryan, S.-A., Wilson, J. A., Heise, A. Anisotropic polymer nanoparticles with solvent and temperature dependent shape and size from triblock copolymers. Polym. Chem. 2019, 10, 3436

  • Jacobs, J., Pavlović, D., Prydderch, H., Moradi,M. A., Ibarboure, E., Heuts, J. P. A., Lecommandoux, S., Heise, A. Polypeptide Nanoparticles Obtained from Emulsion Polymerization of Amino Acid N-Carboxyanhydrides (NCA)J. Am. Chem. Soc. 2019, 141, 12522. 

Star polypeptides for therapeutic delivery 

Star polypeptides were synthesised by dendritic initiation for PPI dendrimers to produce star poly(lysine) with 8 to 64 arms. Explored by collaborators, these materials can form nano-sized polyplexes with DNA and RNA and demonstrated exceptional gene transfection in vitro and in vivo. Star poly(lysine) nanomedicines have been translated to gene delivery for scaffold-guided bone regeneration as well as for the delivery of small therapeutics. This patented technology is currently investigated at a pre-commercialisation stage.   

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bone regenration.png

live image of starLys/pDNA nanoparticles (red) being taken up into MSCs over a 24 h.

Selected publications:

  • Walsh, P. D., Murphy, R., Panarella, A., Raftery, R.M., Cavanagh, B., Simpson, J., O’Brien, F. J., Heise, A., Cryan, S.-A. Bioinspired Star-Shaped Poly(L-Lysine) Polypeptides; Efficient Polymeric Nanocarriers for the Delivery of DNA to Mesenchymal Stem Cells. Mol. Pharm. 2018, 15, 1878. 

  • Walsh, D. P., Heise, A., O’Brien, F. J., Cryan, S.-A. An efficient, non-viral dendritic vector for gene delivery in tissue engineering. Gene Therapy 2017, 24, 681.  

  • Skoulas, D., Stuettgen, V., Gaul, R., Cryan, S.-A., Brayden, D. J., Heise, A. Amphiphilic Star Polypept(o)ides as Nanomeric Vectors in Mucosal Drug Delivery. Biomacromolecules  2020, 21, 2455.

  • O’Dwyer, J., Murphy, R., Dolan, E. B., Kovarova, L. Pravda, M., Velebny, V., Heise, A., Duffy, G. P., Cryan, S.-A. Development of a nanomedicine-loaded hydrogel for sustained delivery of an angiogenic growth factor to the ischaemic myocardium. Drug Deliv. Transl. Res. 2020, 10, 440.

  • Byrne, M., Murphy, R., Kapetanakis, A., Ramsey, J., Cryan, S.-A., Heise, A. Star-Shaped Polypeptides: Synthesis and Opportunities for Delivery of Therapeutics. Macromol. Rapid Comm. 2015, 36, 1862. 

3D shapeable hydrogels from polypeptides

By the choice of amino acids, amphiphilic (star) block copolypeptides can be sythesised, which spontaneously form hydrogels. The group is currently investigating two processing technologies to produce functional 3D materials. The first is 3D printing of physical polypeptide hydrogels. Through optimisation of the copolypetide structure and composition, the Heise group for the first time reported 3D printable biocompatible polypeptide hydrogels with exceptional mechanical strength. Through further rational design, antimicrobial properties were engineered into the hydrogels. The second processing method is 3D moulding of covalent polypeptide organo and hydrogels. These 3D materials hold great promise for the manufacturing of intrinsically antimicrobial 3D tissue engineering scaffolds to match injury geometry.  

physical hydrogels

3D extrusion printing of physical copolypeptide hydrogel

covalent hydrogels

covalent copolypeptide hydrogels

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macroscopic organo-hydrogel

Formation of copolypeptide organogel using bis-triazolinedione (bis-TAD)

Selected publications:

  • Murphy, R., Walsh, D. P., Hamilton, C. A., Cryan, S.-A., in het Panhuis, M., Heise, A. Degradable 3D Printed Hydrogels Based on Star Shaped Copolypeptides. Biomacromolecules 2018, 19, 2691. 

  • Hanay, S. B., O’Dwyer, J., Kimmins, S. D., de Oliveira, F. C. S., Haugh, M.G., O’Brien, F. J., Cryan, S.-A., Heise, A. ACS Macro Letters 2018, 7, 944.

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