In the course of this fiscal year, we have worked on the soluble systems described in the following paragraphs, which constitute attractive targets for the development of pharmaceutical agents. Human cytidine deaminase (CDA). Cytidine deaminase (CDA) is a cytosolic enzyme which catalyzes the hydrolytic deamination of cytidine to uridine. CDA causes also the degradation of several cytidine based compounds potentially active as anticancer or antiviral agents, including the anti-leukemic agent cytosine arabinoside (AraC). In particular, during this fiscal year, we have conducted the research and accomplished the results described in the following paragraphs. 1) Finalized and published a virtual screening for the identification of CDA inhibitors. This work led to the identification of several active compounds, potentially developable into new pharmacological agents for the treatment of leukemia. Moreover, it significantly advanced the current understanding of the molecular mechanisms of nucleotide recognition by CDA. Experimental collaborators: Prof. Alberto Vita and Prof. Silvia Vincenzetti (University of Camerino, Italy). 2) Continued the studies for the identification of novel drug-like CDA inhibitors. Experimental collaborators: Prof. Alberto Vita and Prof. Silvia Vincenzetti (University of Camerino, Italy).

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Costanzi, Stefano; Vilar, Santiago; Micozzi, Daniela et al. (2011) Delineation of the molecular mechanisms of nucleoside recognition by cytidine deaminase through virtual screening. ChemMedChem 6:1452-8
Vilar, Santiago; Chakrabarti, Mayukh; Costanzi, Stefano (2010) Prediction of passive blood-brain partitioning: straightforward and effective classification models based on in silico derived physicochemical descriptors. J Mol Graph Model 28:899-903
Micozzi, Daniela; Pucciarelli, Stefania; Carpi, Francesco M et al. (2010) Role of tyrosine 33 residue for the stabilization of the tetrameric structure of human cytidine deaminase. Int J Biol Macromol 47:471-82
Jiang, Jian-kang; Ghoreschi, Kamran; Deflorian, Francesca et al. (2008) Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550). J Med Chem 51:8012-8