INFORMAZIONI SU
BETTIN Giacomo
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Supervisore:Prof. Brancolini Generation of macrocyclic peptide molecules for cancer therapy |
| Genetic or epigenetic aberrations that affect the HATs/HDACs balance can result in altered gene expression profiles, chromatin remodelling, and changes in nuclear architecture that can ultimately lead to tumour initiation and progression. In humans, the HDAC family comprises multiple members that can be grouped into five subfamilies (I, IIa, IIb, III, and IV) based on their sequence homology and phylogenetic criteria. Although there are numerous HDACs involved in different types and stages of cancer, in this project we will focus exclusively on class IIa HDACs, a subfamily composed of four members: HDAC4, HDAC5, HDAC7, and HDAC9. Aberrant expression of these class IIa HDAC enzymes has been linked to a variety of solid and haematological tumours, and several mouse models have demonstrated their potential oncogenic role. However, most inhibitors developed so far against class IIa HDAC enzymes have shown poor activity or lack of specificity and have failed in vivo. It is therefore important to develop new inhibitors with greater selectivity and efficacy. The use of peptide macrocycles to target these previously unknown binding sites of class IIa HDACs provides a novel approach. If effective, macrocyclic peptides could not only have important therapeutic implications, but also provide insights into the role of specific protein interactions with other proteins, providing better insight into their molecular mechanism in the prognosis and progression of different types of cancer. | |