Polyoxometalates are a class of inorganic compounds characterized by the presence of metallic centers (M), like Mo, W and V, and of other eventual heteroatoms (X) which are surrounded by a specific number of oxygen atoms, and then packed together in a discrete structure. They are well known for their applications in catalysis and material science, and they have recently sparked the interest of the scientific community thanks to their promising biological applications as antibacterial, antiantiviral, antimicrobial, antineurodegenerative and anticancer agents. Their ability to interfere with cellular, bacterial, and viral redox processes and to interact with essential biological macromolecules also highlights their major drawback, which is the lack of selectivity. This thesis focuses on the synthesis of new organic-inorganic polyoxometalate hybrids for specifically targeting cancerous cells and reducing their toxicity toward normal cells. The first part of this work consists in the synthesis of well-known inorganic precursors, in particular bis-substituted tris(NH2) Mn-Anderson-Evans polyoxomolybdates, as well as new compounds such as bis-substituted tris-pentaerythritol Lindqvist polyoxovanadates. The second part of this work is the coupling reactions between the inorganic polyoxometalates (in their activated form with N-hydroxysuccinimide) and biological molecules. A first coupling reaction was performed with an amino acid, L-phenylalanine, in order to optimize the synthetic procedure for the prepared peptides: bombesin and RGD derivatives (in particular Demobesin-1 and c(RGDfK)), whose receptors have proven to be overexpressed on cancerous cells. The introduction of spacers (-EEEEβAla- and -Ttds-) between the polyoxometalate and the bombesin derivative was also evaluated and studied in order to minimize undesired interactions/folding between the two domains and make the peptide more bioavailable. The final products were completely characterized through 5 FT-IR, ESI-MS(-), 1H and 51V NMR (for vanadium compounds), CD, UV-Vis and elemental analysis. Additionally, 2D 1H NMR (COSY, TOCSY and ROESY) were applied to assess composition and secondary structure of the peptide derivatives.

Polyoxometalates are a class of inorganic compounds characterized by the presence of metallic centers (M), like Mo, W and V, and of other eventual heteroatoms (X) which are surrounded by a specific number of oxygen atoms, and then packed together in a discrete structure. They are well known for their applications in catalysis and material science, and they have recently sparked the interest of the scientific community thanks to their promising biological applications as antibacterial, antiantiviral, antimicrobial, antineurodegenerative and anticancer agents. Their ability to interfere with cellular, bacterial, and viral redox processes and to interact with essential biological macromolecules also highlights their major drawback, which is the lack of selectivity. This thesis focuses on the synthesis of new organic-inorganic polyoxometalate hybrids for specifically targeting cancerous cells and reducing their toxicity toward normal cells. The first part of this work consists in the synthesis of well-known inorganic precursors, in particular bis-substituted tris(NH2) Mn-Anderson-Evans polyoxomolybdates, as well as new compounds such as bis-substituted tris-pentaerythritol Lindqvist polyoxovanadates. The second part of this work is the coupling reactions between the inorganic polyoxometalates (in their activated form with N-hydroxysuccinimide) and biological molecules. A first coupling reaction was performed with an amino acid, L-phenylalanine, in order to optimize the synthetic procedure for the prepared peptides: bombesin and RGD derivatives (in particular Demobesin-1 and c(RGDfK)), whose receptors have proven to be overexpressed on cancerous cells. The introduction of spacers (-EEEEβAla- and -Ttds-) between the polyoxometalate and the bombesin derivative was also evaluated and studied in order to minimize undesired interactions/folding between the two domains and make the peptide more bioavailable. The final products were completely characterized through 5 FT-IR, ESI-MS(-), 1H and 51V NMR (for vanadium compounds), CD, UV-Vis and elemental analysis. Additionally, 2D 1H NMR (COSY, TOCSY and ROESY) were applied to assess composition and secondary structure of the peptide derivatives.

Synthesis of polyoxometalates and conjugation with peptides for cancer cell targeting

FRIGO, MATTIA
2021/2022

Abstract

Polyoxometalates are a class of inorganic compounds characterized by the presence of metallic centers (M), like Mo, W and V, and of other eventual heteroatoms (X) which are surrounded by a specific number of oxygen atoms, and then packed together in a discrete structure. They are well known for their applications in catalysis and material science, and they have recently sparked the interest of the scientific community thanks to their promising biological applications as antibacterial, antiantiviral, antimicrobial, antineurodegenerative and anticancer agents. Their ability to interfere with cellular, bacterial, and viral redox processes and to interact with essential biological macromolecules also highlights their major drawback, which is the lack of selectivity. This thesis focuses on the synthesis of new organic-inorganic polyoxometalate hybrids for specifically targeting cancerous cells and reducing their toxicity toward normal cells. The first part of this work consists in the synthesis of well-known inorganic precursors, in particular bis-substituted tris(NH2) Mn-Anderson-Evans polyoxomolybdates, as well as new compounds such as bis-substituted tris-pentaerythritol Lindqvist polyoxovanadates. The second part of this work is the coupling reactions between the inorganic polyoxometalates (in their activated form with N-hydroxysuccinimide) and biological molecules. A first coupling reaction was performed with an amino acid, L-phenylalanine, in order to optimize the synthetic procedure for the prepared peptides: bombesin and RGD derivatives (in particular Demobesin-1 and c(RGDfK)), whose receptors have proven to be overexpressed on cancerous cells. The introduction of spacers (-EEEEβAla- and -Ttds-) between the polyoxometalate and the bombesin derivative was also evaluated and studied in order to minimize undesired interactions/folding between the two domains and make the peptide more bioavailable. The final products were completely characterized through 5 FT-IR, ESI-MS(-), 1H and 51V NMR (for vanadium compounds), CD, UV-Vis and elemental analysis. Additionally, 2D 1H NMR (COSY, TOCSY and ROESY) were applied to assess composition and secondary structure of the peptide derivatives.
2021
Synthesis of polyoxometalates and conjugation with peptides for cancer cell targeting
Polyoxometalates are a class of inorganic compounds characterized by the presence of metallic centers (M), like Mo, W and V, and of other eventual heteroatoms (X) which are surrounded by a specific number of oxygen atoms, and then packed together in a discrete structure. They are well known for their applications in catalysis and material science, and they have recently sparked the interest of the scientific community thanks to their promising biological applications as antibacterial, antiantiviral, antimicrobial, antineurodegenerative and anticancer agents. Their ability to interfere with cellular, bacterial, and viral redox processes and to interact with essential biological macromolecules also highlights their major drawback, which is the lack of selectivity. This thesis focuses on the synthesis of new organic-inorganic polyoxometalate hybrids for specifically targeting cancerous cells and reducing their toxicity toward normal cells. The first part of this work consists in the synthesis of well-known inorganic precursors, in particular bis-substituted tris(NH2) Mn-Anderson-Evans polyoxomolybdates, as well as new compounds such as bis-substituted tris-pentaerythritol Lindqvist polyoxovanadates. The second part of this work is the coupling reactions between the inorganic polyoxometalates (in their activated form with N-hydroxysuccinimide) and biological molecules. A first coupling reaction was performed with an amino acid, L-phenylalanine, in order to optimize the synthetic procedure for the prepared peptides: bombesin and RGD derivatives (in particular Demobesin-1 and c(RGDfK)), whose receptors have proven to be overexpressed on cancerous cells. The introduction of spacers (-EEEEβAla- and -Ttds-) between the polyoxometalate and the bombesin derivative was also evaluated and studied in order to minimize undesired interactions/folding between the two domains and make the peptide more bioavailable. The final products were completely characterized through 5 FT-IR, ESI-MS(-), 1H and 51V NMR (for vanadium compounds), CD, UV-Vis and elemental analysis. Additionally, 2D 1H NMR (COSY, TOCSY and ROESY) were applied to assess composition and secondary structure of the peptide derivatives.
Polyoxometalates
Conjugation
Cancer
Peptides
Tumor
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12608/41670