I am a second-year Ph.D. student at the Department of Chemical Sciences of the University of Padua under the supervision of Barbara Biondi and Fernando Formaggio. My Ph.D. Project takes place in close collaboration with Fresenius Kabi iPSUM, a company engaged in the large-scale synthesis of peptides at its facilities in Villadose (Rovigo, Italy). I am focused on the development of innovative and green industrial processes for the production of peptide-based APIs. To this end, I have been working on the synthesis of peptides by using green reagents and solvents [1-4] and exploiting strategies that allow the reduction of waste and the use of environment friendly chemicals.

From March to August 2024, I had the opportunity to work for 6 months in Prof. Fernando Albericio’s lab, at the University of KwaZulu-Natal in South Africa, thanks also to a generous EPS mobility fellowship. Prof. Albericio is a worldwide recognized leader in the fields of innovative synthetic protocols, of environmentally sustainable solvents and reagents, and of waste reduction in peptide synthesis. In his lab I was involved in two different projects, one about the use of green solvent mixtures in common SPPS, the other concerning the use of refractometry to monitor in real time the various steps of peptide synthesis.

The first project aimed at evaluating different types of green solvent mixtures in the synthesis of a model tetrapeptide. In all protocols greener reagent were used instead the common ones (e.g. 4-methylpiperidine instead of piperidine) and washes after coupling were avoided. The use of a different Fmoc removal strategy, known as in-situ Fmoc removal, was evaluated as well. All protocols led to optimal results, comparable to those obtained in DMF [5].

In the second project I used refractometry as a PAT (Process Analytical Tool) to monitor in real time the steps (deprotection, coupling and washing) of SPPS, carried out in different solvents and solvent [6] mixtures. Refractometry is sensitive to the mass transfer from the solid support to the solution or vice versa. Therefore, the endpoint of a reaction can be determined and the synthetic process in use can be optimized accordingly. Through the evaluations carried out during this research period (paper in preparation), we can confirm that DMF is a very efficient solvent in peptide synthesis, but the use of green solvents brings comparable results.

During the internship in South Africa, I had the opportunity to work with two leaders in peptide science, Prof. Fernando Albericio and Prof. Beatriz G. de la Torre. They taught me a lot and they were always supportive. I thank them and all the members of the research group who always helped me with friendliness. Finally, I am grateful to the European Peptide Society for funding my research period in South Africa. I strongly recommend all young researchers to carry out an internship abroad to increase their scientific and cultural background, since they have currently the opportunity of being supported by an EPS Mobility Fellowship.

 

Members of F. Albericio and B.G. de la Torre’s lab.

 

Prof. F. Albericio, Luana Lastella and Prof. B.G. de la Torre (left to right) at the
37th European Peptide Symposium (Florence, 2024).

References:

1.  Albini, F., Biondi, B., Lastella, L., & Peggion, C. (2023). Oxime and thiazolidine chemoselective ligation reactions: a green method for cotton functionalization. Cellulose, 30, 5573-5587
2. Peggion, C., Panetta, V., Lastella, L., Formaggio, F., Ricci, A., Oancea, S., Hilma, G., & Biondi, B. (2024). Relevance of amphiphilicity and helicity on the antibacterial action of a histatin 5-derived peptide. J. Pept. Sci., 30, e3609.
3. Cocîrlea, M.D., Simionescu, N., Petrovici, A.R., Silion, M., Biondi, B., Lastella, L., & Oancea, S. (2024). In Vitro Screening of Ecotoxic and Cytotoxic Activities of Ailanthus altissima Leaf Extract against Target and Non-Target Plant and Animal. Int. J. Mol. Sci., 25, 5653.
4. Chinellato, M., Perin, S., Carli, A., Lastella, L., Biondi, B., Borsato, G., Di Giorgio, E., Brancolini, C., Cendron, L., & Angelini, A. (2024). Folding of Class IIa HDAC Derived Peptides into α-helices Upon Binding to Myocyte Enhancer Factor-2 in Complex with DNA. J. Mol. Bio., 436,168541.
5. Noki, S., Lastella, L., Serban, S., Basso, A., Orosz, G., de la Torre, B. & Albericio, F. (2024). Triethyl Phosphate (TEP) – Dimethylsulfoxide (DMSO), as Green Solvent Mixture for Solid- Phase Peptide Synthesis (SPPS), accepted with minor revisions.
6. De La Torre, B.G., Ramkisson, S., Albericio, F., & Lopez, J. (2021). Refractive Index: The Ultimate Tool for Real-Time Monitoring of Solid-Phase Peptide Synthesis. Greening the Process. Org. Process Res. Dev., 25, 1047-1053.