chiara pelosi

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Maria Rosaria Tinè

Synthesis, biochemical and biophysical evaluation of novel protein-polymer conjugates with enhanced stability.

Protein-polymer conjugates combine the biological functions of protein drugs with the convenient handling of synthetic polymers. Nowadays several of such biohybrids are successfully used to treat some diseases, because the covalent attachment of the polymer improves the pharmacokinetics of the protein-based drugs, resulting in a major life-time of the drug in the body of the patients.
The PhD project is divided in two main field.
The first field (in collaboration with Dr. Frederik Wurm, Max Planck Institute of Polymer Research, Mainz) concerns the critical design, synthesis, characterization and biochemical evaluation of novel protein-polymer conjugates, based on poly(phosphoester)s, a promising class of polymer, potential alternative for poly(ethylene glycol) (PEG), the most common polymer used in the bioconjugation field. A wide set of conjugates will be synthesized (with a variable degree of polymer length and grafting), and their activity and thermal stability will be evaluated, with the help of techniques as Nano-Differential Scanning Calorimetry, Nano-Differential Scanning Fluorimetry and circular dichroism. The biodegradability and biocompatibility of the samples in simulated human fluids will be tested, and the more promising samples will be tested in vivo.
The second field concerns a more fundamental study, a biophysical evaluation on how the polymer influence the structure and the dynamics of the protein at which is covalently linked. As a matter of facts, the protein functionality is strictly linked to its dynamics, that presents characteristic fluctuations from the milliseconds to the picoseconds time-scale. The main techniques that will be used for our purposes are Neutron Scattering spectroscopy (in collaboration with Dr Daniela Russo, Institute Laue Langevin, Grenoble) and Differential Scanning Calorimetry (in collaboration with Dr Elpidio Tombari, CNR Pisa), used with a complementary approach.

Title: “Thermodynamic Stability of Myoglobin-Poly(Ethylene Glycol) Bioconjugates: a Calorimetric Study”. Authors: Chiara Pelosi, Francesca Saitta, Frederik Wurm, Maria Rosaria Tinè, Celia Duce and Dimitrios Fessas; published on Thermochimica Acta, November 2018.

Title: “PPE-ylation of proteins: synthesis, activity and stability of myoglobin-polyphosphoesters conjugates”. Authors: Chiara Pelosi, Celia Duce, Daniela Russo, Maria Rosaria Tinè and Frederik R. Wurm; published on European Polymer Journal, September 2018.

Oral communications at congress:
Title: “Evaluation of thermal stability of model protein-polymer conjugates” presented to the XL National Congress on Calorimetry, Thermal Analysis and Applied Thermodynamics, Pisa (Italy), December 2018.

Title: “How the protein Myoglobin is affected by the covalent attachment of new biodegradable polymers” presented to the XIV International Symphosium on Inorganic Biochemistry–ISIB, Wroclaw (Poland), September 2018.

Title: “Protein polymer conjugates: from the structure to the function” presented to the XLVI Congresso SCI della Divisione di Chimica Fisica Italiana, Bologna (Italy), June 2018.

Title: “Synthesis and characterization of novel protein-polymer conjugates based on biodegradable polyphosphoesters”; presented to the 13th Mediterranean Conference on Calorimetry and Thermal Analysis – Medicta 2017, Loano (Italy), September 2017.

Title: “New development in protein-polymer conjugation: PPE-ylated myoglobin”; presented to the 4th Central and Eastern European Conference on Thermal Analysis and Calorimetry-CEEC-TAC4, Chisinau (Moldova), August 2017.

Poster communications at congress:
Title: “Protein-polymer Conjugation: the gold standard PEG vs biodegradable poly(phosphoester)s”; presented to the congress Chemistry for the Future 2018- CFF 2018, Pisa (Italy), July 2018.

Title: “Critical evaluation of a model protein-polymer conjugate: from a microscopic-scale to the interaction with human fluids”; presented to the congress Chemistry for the Future 2019-CFF 2019, Pisa (Italy), July 2019. Winner of the best poster award.