MRNA CAP SYNTHESIS--A NOVEL ANTIFUNGAL DRUG TARGET

描述：(摘自申请者的摘要)真菌病原体 对各种疾病负责，从无害的皮肤 真菌对危及生命的系统性感染的影响。近几年来， 严重真菌感染的数量显著增加，原因是 越来越多的免疫抑制和免疫受损的个人， 如艾滋病患者、移植受者和化疗或 放射治疗患者。有效无毒的抗真菌药物 很难辨认，部分原因是人类和 真菌是真核生物，有许多共同的潜在分子靶点。 目前使用的大多数抗真菌药物对有限数量的靶点起作用 主要在真菌细胞表面发现。迫切需要 更多的抗真菌药物，特别是那些针对新靶点的药物。 翻译靶向疗法特别受欢迎，因为 它们在治疗细菌感染方面已被证明具有价值。这项建议 描述了一种用于鉴定新的抗真菌药物的新型高通量筛选 专门针对蛋白质翻译的药物。化验结果 通过选择性地识别翻译抑制物的能力 抑制正常蛋白质所需的RNA结构的合成 综合。计划进行二次化验以验证真菌的特异性 翻译。初步结果支持该提案的理念。 建议的商业应用：不可用

DESCRIPTION: (Adapted from the applicant's abstract) Fungal pathogens are responsible for a variety of diseases ranging from innocuous dermal mycoses to life-threatening systemic infections. In recent years, the number of serious fungal infections has increased markedly as a result of the growing number of immunosuppressed and immunocompromised individuals, such as AIDS patients, transplant recipients, and chemotherapy or radiotherapy patients. Efficacious and non-toxic antifungal therapeutics are difficult to identify, in part due to the fact that both humans and fungi are eukaryotes and share many potential molecular targets in common. Most antifungals currently used act against a limited number of targets found primarily on the fungal cell surface. An urgent need exists for more antifungal agents, especially those acting against new targets. Translation-targeted therapeutics are particularly desirable because of their proven value in treating bacterial infections. This proposal describes a novel high-throughput screen for identifying new antifungal agents specifically targeted against protein translation. The assay identifies translational inhibitors by their ability to selectively inhibit the synthesis of an RNA structure required for normal protein synthesis. Secondary assays are planned to verify specificity for fungal translation. Preliminary results support the concept of the proposal. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE