Toward a clinical antifungal peptoid: Investigations into the therapeutic potential of AEC5.
Toward a clinical antifungal peptoid: Investigations into the therapeutic potential of AEC5.
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DOI：
10.1002/bip.23276
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发表时间：
2019-04
期刊：
影响因子：
2.9
通讯作者：
Sabrina K. Spicer;A. Subramani;Angelica L. Aguila;R. M. Green;Erin E. McClelland;Kevin L. Bicker
中科院分区：
文献类型：
--
作者：
Sabrina K. Spicer;A. Subramani;Angelica L. Aguila;R. M. Green;Erin E. McClelland;Kevin L. Bicker
新生隐球菌是一种真菌病原体，可在免疫功能低下的人中引起隐球菌性脑膜炎。现有的抗真菌治疗计划具有较高的哺乳动物毒性和不断增加的耐药性，表明迫切需要新的无毒治疗药物。抗菌肽是解决这一问题的一种选择。我们的实验室最近发现了一种三肽类化合物，AEC5，对新生葡萄球菌具有良好的疗效和选择性。在此，我们报道了该化合物的广谱功效、杀灭动力学、作用机制、体内半衰期和亚慢性毒性的研究。最值得注意的是，这些研究表明，AEC5迅速减少真菌负担，在3小时内杀死所有活着的真菌。此外，AEC5在体内的半衰期为20+小时，每天注射28天后没有观察到体内毒性。这项研究代表了AEC5作为一种实用的治疗新生葡萄球菌感染的选择的特征的重要一步。
Cryptococcus neoformans is a fungal pathogen that causes cryptococcal meningitis in immunocompromised individuals. Existing antifungal treatment plans have high mammalian toxicity and increasing drug resistance, demonstrating the dire need for new, nontoxic therapeutics. Antimicrobial peptoids are one alternative to combat this issue. Our lab has recently identified a tripeptoid, AEC5, with promising efficacy and selectivity against C. neoformans. Here, we report studies into the broad-spectrum efficacy, killing kinetics, mechanism of action, in vivo half-life, and subchronic toxicity of this compound. Most notably, these studies have demonstrated that AEC5 rapidly reduces fungal burden, killing all viable fungi within 3 hours. Additionally, AEC5 has an in vivo half-life of 20+ hours and no observable in vivo toxicity following 28 days of daily injections. This research represents an important step in the characterization of AEC5 as a practical treatment option against C. neoformans infections.