Small Molecule Blockers of B. anthracis Toxin

描述（由申请方提供）：本SBIR提案的总体目标是鉴定能够通过阻断由毒素的保护性抗原组分形成的跨膜孔来阻断炭疽杆菌致死毒素的细胞毒性作用的小分子。这些分子被设想用作治疗炭疽的药物。鉴定此类化合物的策略包括开发用于测试化合物抑制炭疽毒素的细胞毒性作用的能力的测定法。将设计和合成有限的代表性化合物库。然后将测试合成的化合物的抑制活性。由此产生的基线数据将用于计算机辅助设计对跨膜孔具有改进亲和力的化合物，然后进行第二轮化学合成和测试。

DESCRIPTION (provided by applicant): The overall goal of this SBIR proposal is the identification of small molecules capable of blocking the cytotoxic action of Bacillus anthracis lethal toxin by blocking the transmembrane pore formed by the protective antigen component of the toxin. Such molecules are envisioned for use as drugs for the treatment of anthrax. The strategy to identify such compounds involves developing an assay for testing the ability of compounds to inhibit the cytotoxic effect of anthrax toxin. A limited representative library of compounds will be designed and synthesized. The synthesized compounds will then be tested for inhibitory activity. The resulting baseline data will be used for computer-assisted design of compounds with improved affinity towards the transmembrane pore, followed by a second round of chemical synthesis and testing.