Theoretical Studies of Bacterial Ribosome Antagonists

细菌核糖体拮抗剂的理论研究

• 批准号: 6403809
• 负责人: WILLIAM D ARNOLD
• 金额: $ 3.33万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6403809
• 关键词: aminoglycoside antibiotics; bacteria; binding sites; cell component structure /function; chemical association; chemical structure function; computer graphics /printing; computer program /software; cytotoxicity; drug design /synthesis /production; genetic translation; inhibitor /antagonist; intermolecular interaction; ionic bond; mathematical model; model design /development; molecular biology information system; molecular dynamics; molecular energy level; nucleic acid structure; physical model; ribosomal RNA; ribosomal proteins; ribosomes; structural biology; thermodynamics

We propose a computational investigation of the interaction of aminoglycoside antibiotics with the 30S ribosomal subunit. These compounds are inhibitors of bacterial translation, and are among the oldest known antibiotics. As a consequence of their age and wide use, they are subject to an increasing array of bacterial resistance. In addition, although they specifically target the bacterial ribosome, they also act to a lesser extent against the eukaryotic ribosome, resulting in human toxicity. The recently solved atomic resolution structure of the bacterial 30S ribosome, both free and complexed with three aminoglycoside antibiotics, provides us with an unprecedented opportunity to design new drugs for which bacterial resistance factors have not yet arisen, and which are not as toxic to patients.

我们提出了氨基糖苷抗生素与30S核糖体亚基的相互作用的计算研究。这些化合物是细菌翻译的抑制剂，是最古老的已知抗生素之一。由于它们的年龄和广泛使用，它们会受到越来越多的细菌耐药性。此外，尽管它们专门针对细菌核糖体，但它们的作用也较小，对真核核糖体的作用，导致人类毒性。最近求解的30S核糖体的原子分辨率结构，无论是免费且与三种氨基糖苷抗生素复合，为我们提供了前所未有的机会，可以设计新药物，这些新药尚未出现，这些药物尚未引起细菌抗性因素，并且对患者不毒性。