Tumor targeting

The use of peptides or peptidomimetics appears as a privileged option to develop small molecules targeting tumor specific antigens involved in protein-protein interactions (PPI). This approach poses a whole new set of challenges to chemists for the design and synthesis of new effector molecules and targeting moieties with the potential of being evolved in therapeutic and diagnostic tools in oncology.
In this project, we have collected different types of expertise to take up some of these challenges, focusing on a selected group of related and well characterized targets relevant in cancer biology that can be addressed using peptidomimetics or nonnatural oligomers folding into well-defined structures (foldamers). Our strategy builds on previous knowledge on the design, synthesis and characterization of peptidomimetics capable of reproducing short peptide pharmacophoric fragments of PPI, and of foldamers able to mimic elements of protein secondary structure.
The project will focus on chemistry-driven approaches towards tumor targeting peptidomimetics, peptide foldamers and small molecule drug (or imaging agent) conjugates, either covalently linked or noncovalently assembled in nanoscaled devices. Synthetic organic chemistry, peptide chemistry, computational modeling, spectroscopic analysis, nanotechnology, pharmacology and molecular biology will be involved to accomplish the following strategic objectives.
1. Identification of tumor targeting peptidomimetics and foldamers (PPI inhibitors)
2. Synthesis of small molecule – drug conjugates for tumortargeted therapy (or diagnosis via imaging agents)
3. Synthesis of multimeric and nanoscaled systems for drug delivery and cancer imaging
4. Synthesis and study of peptides and foldamers controlling tumors via immunemodulation or peptidemembrane interactions
In the past three years the PI and AIs of the present proposal have collaborated within a 2010-11 funded PRIN network expiring at the end of January 2016. The level of integration of the various units is demonstrated by the numerous (37) recently published joint research papers and by the organization of an International Symposium on these themes as the final scientific event of the project (https://events.unibo.it/bolognapeptides2016).

The development of novel chemistry-driven approaches toward tumor targeting, such as those proposed here, will have a major impact on the fight against cancer. Although the budget requested is clearly underestimated for such a huge research effort (mainly due to budget restrictions for the entire 2015 PRIN program), we plan to use it to synergize the 9 research units and reach the critical mass in terms of human capital (including PhD students and postdocs present in the various units and to be recruited with the present grant), expertise and research infrastructures in order to be able to compete internationally with wellestablished research groups.

Participants

GENNARI

ZANARDI

GENTILUCCI

FORMAGGIO

OCCHIATO

COLOMBO

STELLA

PIARULLI

MANZONI

Funding

We thank MIUR Proj. 20157WW5EH for financial support