Molecular modeling of soluble proteins

在本财政年度中，我们致力于以下各段所述的可溶性体系，这些体系构成了药物制剂发展的有吸引力的目标。 人胞苷脱氨酶(CDA)。胞苷脱氨酶(CDA)是一种催化胞苷水解脱氨基生成尿苷的胞浆酶。CDA还会导致几种可能具有抗癌或抗病毒活性的胞苷类化合物的降解，包括抗白血病药阿糖胞苷(AraC)。 特别是，在本财政年度，我们进行了研究，并取得了以下各段所述的成果。 1)完成并公布了用于鉴定CDA抑制剂的虚拟筛选。这项工作导致了几种活性化合物的鉴定，这些化合物可能会被开发成治疗白血病的新的药理药物。此外，它还极大地促进了目前对CDA识别核苷酸的分子机制的理解。实验合作者：Alberto Vita教授和Silvia Vincenzetti教授(意大利卡梅里诺大学)。 2)继续进行新的类药物CDA抑制剂的鉴定研究。实验合作者：Alberto Vita教授和Silvia Vincenzetti教授(意大利卡梅里诺大学)。

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).