Paiardini Alessandro

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Dipartimento di Scienze Biochimiche "A. Rossi Fanelli"




tel: 0649917700

Informazioni personali
Informazioni personali: 

Dr. Alessandro Paiardini has a consolidated national and international reputation as an expert in Computational Structural Biology and Drug Design. His research unit is interested in many aspects of protein chemistry, including folding, evolution and structure-function relationship of proteins and macromolecular assemblies. In particular, his research interests concern protein interaction with small molecules and inhibitors. Specific binding interactions between small molecules and proteins are of pivotal importance to many biological processes. Since a great number of human diseases results from an alteration of such interactions, it is not surprising that most drugs act by binding to a target protein and modulating its activity and affinity for other ligands. In the past years, a number of protein candidates for the development of therapeutic agents has been the target of his research.

During his career, he undertook a number of studies aimed at understanding at a molecular level the structure/function relationship, ligand binding, catalytic mechanism, evolution, and folding of Pyridoxal-5’-phosphate dependent enzymes. The latter comprise a series of protein targets for the development of therapeutic agents, which were subject of investigation: SHMT (tumors and malaria); Threonine aldolase and Alanine racemase (antimicrobial and antifungal targets); Alanine:glyoxylate aminotransferase (primary hyperoxaluria type I); Cystalysin (adult periodontitis); DDC (Parkinson's desease); GAD65 (Type-1 diabetes).


Malaria is a parasitic disease that remains a global health burden. The ability of the parasite to rapidly develop resistance to therapeutics drives an urgent need for the delivery of new drugs. In collaboration with the research group of Dr. Sheena McGowan (Monash University, Australia), Dr. Paiardini has contributed to the discovery of the most potent in vitro and in vivo inhibitors available so far of the anti-malarial drug targets PfA-M1 and PfA-M17 aminopeptidases, as documented in the publication records.


Dr. Paiardini and his group and collaborators (Prof. Cutruzzolà, Sapienza University) contributed to obtain structure and mechanistic studies on selected enzymes involved in biofilm formation, to date poorly characterized despite their biomedical relevance. Integration of computational and experimental approaches allowed the identification of structural determinants controlling the interaction of selected enzymes with small molecules (such as c-di-GMP, nucleotides and metals) and inhibitors, which were designed and synthesized thanks to fruitful collaborations with medicinal chemists (Prof. Cappellacci, University of Camerino).


In the last years, Dr. Paiardini and his collaborators (Prof. Cutruzzolà, Prof. Contestabile, Sapienza University) focussed on the role of enzymes whose proper function is crucial for healthy cell proliferation. In this ground, he contributed to define the role of SHMT (a studied target for anticancer therapies) protein dynamics upon cofactors, substrates and inhibitors binding.  Also, in collaboration with medicinal chemists of Pittsburgh (Prof. McDermott, Dr. Koes), he rationally designed compounds able to inhibit SHMT. Moreover, Dr. Paiardini and his collaborators (Dr. Guarguaglini, CNR) have provided the first Protein-Protein Interaction (PPI) inhibitors of the Aurora-A/TPX2 complex (implicated in the assembly and maintenance of the mitotic spindle), paving the way for the development of new anti-cancer strategies.




Bioinformatica e Farmacologia - Biotecnologie L3 - Farmacia e Medicina, SSMMFFNN

Structure, Function and Biosynthesis of Proteins (English) - Genetics and Molecular Biology - SSMMFFNN

Biochemistry (English) - Bioinformatics - Farmacia e Medicina, SSMMFFNN, 3I

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