Synthetic strategies towards short-chain peptides for potential biomedical applications and tumor-targeted mesoporous silica-based drug delivery systems development

Abstract

My PhD research project was focused on the design and development of short-chain peptides with biomedical applications and on the identification of new peptide synthesis strategies. Briefly, the specific objectives of my research work were the following: · Design and synthesis of novel methylated tetrapeptides acting as leptin antagonists with potentially improved stability and pharmacokinetic properties compared to the non-methylated analogue leptin antagonist LDFI. · Identification and synthesis of a novel peptide ligand able to recognize CD38, a marker overexpressed on multiple myeloma (MM) cells, for the targeted delivery of bortezomib, the drug of choice for this type of cancer. · Design and synthesis of new peptide entities to use as inhibitors linked to chelators to produce new molecular probes for prostate cancer imaging via PET. · Identification of new and efficient peptide synthesis strategies aimed at obtaining small peptides in the solution phase. The developed strategies can prove useful for obtaining biologically active peptides. · Development of a targeted MSN-based nanocarrier bearing the anticancer drug doxorubicin and grafted, on the external surface, with folic acid (FOL-MSN-DOXO). The system developed in this study provides an attractive template to develop more selective DOXO delivery systems by using peptides as targeting ligands. The present thesis consists of published work (papers) and work in progress (ongoing works) that must still be completed in order to be published in the future. Peptide sequences and their structural characterizations have been omitted in ongoing work 1 and in ongoing work 2 since a patent application is going to be filed for both products.