NEW METHOD FOR QSAR FOR BIOPHARMACEUTICAL PRODUCTS

生物制药产品 QSAR 的新方法

• 批准号: 6525352
• 负责人: BORIS Y ZASLAVSKY
• 金额: $ 20.73万
• 依托单位: ANALIZA, INC.
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6525352
• 关键词: acidity /alkalinity; analytical chemistry; biological products; biotherapeutic agent; chemical structure function; drug design /synthesis /production; drug discovery /isolation; drug screening /evaluation; hydropathy; method development; peptides; protein structure function

We propose to develop a new methodology for measurement of hydrophobic properties of therapeutic agents. This information is important for Quantitative Structure-Activity Relationships (QSAR) analyses. While the QSAR analysis is widely used for common drugs, it is virtually non-existent for various technical reasons for biological agents. The new methodology should provide information useful for QSAR of bio pharmaceuticals as well as for small compounds. The technique is based on a novel analytical application of partitioning in aqueous polymer two- phase systems. The methodology is unique (regarding the type of information obtained). quantitative and universal (may be used for comparison of compounds of different chemical nature), inexpensive and easy to perform. It thus provides a viable option for obtaining relevant structure-related information during screening early in the discovery process. The principal objective of the Phase II portion is to further develop and validate the technology for a wide variety of biotherapeutical agents, with specific emphasis on peptides, and for common drugs. Additional objectives include evaluation of the technique for analysis of various structural modifications, development of recommended systems and assay conditions, examination of technical issues related to screening applications, development of an automated measurement workstation. and incorporation of the data into modern QSAR techniques. PROPOSED COMMERCIAL APPLICATION: New relevant information useful for Quantitative Structure-Activity Relationships (QSAR) analysis of therapeutic agents should help improve the rational drug design process. A fast and inexpensive evaluation of an important structure-related descriptor as proposed should help the design of biopharmaceuticals and common drugs of improved efficacy and safety.

我们建议开发一种新的方法来测量治疗剂的疏水性。此信息对于定量构效关系 (QSAR) 分析非常重要。虽然 QSAR 分析广泛用于常见药物，但由于各种技术原因，它对于生物制剂实际上不存在。新方法应该为生物制药以及小化合物的 QSAR 提供有用的信息。该技术基于水性聚合物两相系统中分配的新颖分析应用。该方法是独特的（关于获得的信息类型）。定量且通用（可用于比较不同化学性质的化合物）、廉价且易于执行。因此，它为在发现过程早期的筛选过程中获取相关结构相关信息提供了可行的选择。 II 期部分的主要目标是进一步开发和验证各种生物治疗药物（特别是肽）和常见药物的技术。其他目标包括评估各种结构修饰分析技术、开发推荐系统和测定条件、检查与筛选应用相关的技术问题、开发自动测量工作站。并将数据纳入现代 QSAR 技术。拟议的商业应用：可用于治疗药物定量构效关系（QSAR）分析的新相关信息应有助于改进合理的药物设计过程。对所提出的重要结构相关描述符进行快速且廉价的评估应有助于设计提高功效和安全性的生物制药和普通药物。