ESR7: Vincenzo Di Lorenzo
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Host Organization
Medicinal Chemistry Research Group Research Center for Natural Sciences Hungary Supervisors Dr. György M. Keserű Consultants Dr. György G. Ferenczy Dr. Péter Ábrányi-Balogh 
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Design and synthesis of covalent allosteric probes Most current drugs are designed to bind directly to the primary active sites (also known as orthosteric sites) of their biological targets. Allosteric modulators offer a powerful yet underexploited therapeutic approach. Covalent inhibitors have enjoyed a long history in drug discovery. Due to the improved design principles, in the past few years the number of successful research projects concerning covalent inhibitors has been rapidly increasing. In this project, our goal is to identify and characterize covalent allosteric modulators of therapeutically relevant protein targets. Our objectives are developing experimental and computational tools to analyze and predict druggable allosteric sites suitable for covalent targeting, followed by designing the workflows for optimizing covalent allosteric probes. Finally, we synthesize and investigate high affinity and specific covalent probes for the identification of allosteric pockets on selected protein targets. Our approach is based on a combination of experimental and computational techniques, including fragment screening with structural characterization (X-ray, NMR, H/D exchange), proteomics (MS/MS), virtual screening, synthetic and medicinal chemistry. The identification of allosteric binding sites will be performed experimentally, e.g. by the application of a carefully designed photoactivable pharmacophore library. The newly identified sites will be explored by experimental and virtual screening of covalent fragment libraries. Viable chemical starting points identified this way will be subjected to fragment based optimization leading fully functional allosteric modulators.
This research will be focused to target pharmacologically relevant proteins in oncology (e.g. oncogenic enzymes like the mutant variants of KRAS, Histone Deacetylase 8 and the SHP2 phosphatase) and in psychiatry (e.g. neurotransmitter G-protein coupled receptors). |
Brief Scientific Bio
I graduated in Medicinal Chemistry and Pharmaceutical technology (MSc) at Federico II University with full mark. My thesis was conducted in Gröningen (the Netherlands) under the supervision of Prof. Alexander Dömling and the PhD Jingayo Li, here, I developed essential and deep organic and medicinal chemistry skills, exploring the efficacy and utility of MCRs in Drug Design as well as broadening the applicability of coupling reagents for cyclization purposes. In Naples’s Labs (Rimoli M. G.) I applied microwaves, ultrasounds and one-pot strategies for Medicinal and Green chemistry purposes working on the synthesis of imdazo[1,2b]pyridazines.
Following these,I participated in other 2 Erasmus Traineeship Projects:
-at IQAC (Triola G., Barcelona, Spain) working on synthesis and development of hydroxilamines as new accountable probes for fatty acid detection and on performing new synthetic strategies for Acrylodane
-at HHU (Stark H., Düsseldorf) I explored the strategies and the challenges of synthetic procedures and design of new multitarget drugs, in particular for the treatment of glaucoma and other H3 associated pathologies.
I have now joined the Medicinal chemistry Group of Prof. Dr. Keseru at the Research Center for Natural Sciences, Hungary as a Ph.D. candidate to work on allosteric drug modulator development for cancer and psychiatry treatment.
I graduated in Medicinal Chemistry and Pharmaceutical technology (MSc) at Federico II University with full mark. My thesis was conducted in Gröningen (the Netherlands) under the supervision of Prof. Alexander Dömling and the PhD Jingayo Li, here, I developed essential and deep organic and medicinal chemistry skills, exploring the efficacy and utility of MCRs in Drug Design as well as broadening the applicability of coupling reagents for cyclization purposes. In Naples’s Labs (Rimoli M. G.) I applied microwaves, ultrasounds and one-pot strategies for Medicinal and Green chemistry purposes working on the synthesis of imdazo[1,2b]pyridazines.
Following these,I participated in other 2 Erasmus Traineeship Projects:
-at IQAC (Triola G., Barcelona, Spain) working on synthesis and development of hydroxilamines as new accountable probes for fatty acid detection and on performing new synthetic strategies for Acrylodane
-at HHU (Stark H., Düsseldorf) I explored the strategies and the challenges of synthetic procedures and design of new multitarget drugs, in particular for the treatment of glaucoma and other H3 associated pathologies.
I have now joined the Medicinal chemistry Group of Prof. Dr. Keseru at the Research Center for Natural Sciences, Hungary as a Ph.D. candidate to work on allosteric drug modulator development for cancer and psychiatry treatment.
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This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 956314.
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