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。这一信息对定量构效关系（QSAR）分析具有重要意义。虽然QSAR分析广泛用于普通药物，但由于各种技术原因，它实际上不存在于生物制剂中。新方法将为生物药品和小化合物的QSAR提供有用的信息。该技术是基于在水相聚合物两相体系中分配的一种新的分析应用。方法是独特的（关于所获得的信息类型）。定量和通用（可用于不同化学性质的化合物的比较），价格低廉，易于操作。因此，它为在发现过程的早期筛选过程中获得相关结构相关信息提供了一种可行的选择。第二阶段的主要目标是进一步开发和验证各种生物治疗药物的技术，特别强调多肽和普通药物。其他目标包括评估分析各种结构变化的技术，开发推荐的系统和分析条件，检查与筛选应用相关的技术问题，开发自动化测量工作站。并将数据纳入现代QSAR技术。建议的商业应用：对治疗药物定量构效关系（QSAR）分析有用的新相关信息应有助于改善合理的药物设计过程。对一个重要的结构相关描述符进行快速和廉价的评估，将有助于设计具有更高疗效和安全性的生物制药和普通药物。