SYNTHESIS OF CARDIOVASCULAR POLYETHER ANTIBIOTICS

心血管聚醚抗生素的合成

• 批准号: 2392589
• 负责人: WILLIAM C STILL
• 金额: $ 31.91万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2392589
• 关键词: antibiotics; cardiovascular agents; chemical binding; chemical models; chemical structure function; computer simulation; drug design /synthesis /production; drug screening /evaluation; ion transport; ionophores; monensin; neurotransmitter receptor

Naturally occurring polyether ionophores (e.g. lasalocid, monensin) have important inotropic properties. It is believed that these properties are a function to the ability of such molecules to bind and transport cations across biological membranes. The objective of this proposal is to develop powerful methods by which new, artificial ionophores which have highly selective cation-binding and transporting properties may be designed and prepared. Previous work has shown that the highest selectivity for binding closely related cations is found with ionophores which have limited conformational flexibility. In this application, I propose designs and syntheses of a series of new, podand ionophores which are conformationally homogeneous nd thus are more rigid than most previously studied ionophores. We will determine the three-dimensional structures and binding properties of these new ionophores in order to establish the relationship between their chemical structures and ionophoric properties. We will use the data obtained to validate a computational method using free energy perturbation for predicting the ionophoric properties of new ionophores. A key goal of this proposal is to develop a reliable computational tool which allows hypothetical designs for new ionophores to be tested by a calculation for their ion- binding or transporting properties. Such a tool would allow the design of optimally selective new ionophores prior to time-consuming synthesis.

天然存在的聚醚离子载体（如激光酸、莫能菌素）具有

项目成果

Engineering of a synthetic receptor to alter peptide binding selectivity.

改造合成受体以改变肽结合选择性。

• DOI: 10.1016/1074-5521(95)90270-8
• 发表时间: 1995
• 期刊: Chemistry & biology
• 作者: Carrasco,MR;Still,WC
• 通讯作者: Still,WC