链霉菌属 17944 产生的替兰霉素抑制丝虫天冬酰胺 tRNA 合成酶。
Tirandamycins from Streptomyces sp. 17944 inhibiting the parasite Brugia malayi asparagine tRNA synthetase.
机构信息
Department of Chemistry, Scripps Florida, Jupiter, Florida 33458, USA.
出版信息
Org Lett. 2011 Apr 15;13(8):2034-7. doi: 10.1021/ol200420u. Epub 2011 Mar 15.
Abstract
Lymphatic filariasis is caused by the parasitic nematodes Brugia malayi and Wuchereria bancrofti, and asparaginyl-tRNA synthetase (AsnRS) is considered an excellent antifilarial target. The discovery of three new tirandamycins (TAMs), TAM E (1), F (2), and G (3), along with TAM A (4) and B (5), from Streptomyces sp. 17944 was reported. Remarkably, 5 selectively inhibits the B. malayi AsnRS and efficiently kills the adult B. malayi parasite, representing a new lead scaffold to discover and develop antifilarial drugs.
摘要
淋巴丝虫病是由寄生线虫班氏吴策线虫和马来丝虫引起的，而天冬酰胺-tRNA 合成酶（AsnRS）被认为是一种极好的抗丝虫靶点。从链霉菌 17944 中发现了三种新型替兰霉素（TAMs），即 TAM E（1）、F（2）和 G（3），以及 TAM A（4）和 B（5）。值得注意的是，5 选择性抑制班氏吴策线虫的 AsnRS 并有效杀死成年班氏吴策线虫寄生虫，代表了发现和开发抗丝虫药物的新先导骨架。
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