Using Dendrimers to Design Multivalent Therapeutic Agent

使用树枝状聚合物设计多价治疗剂

• 批准号: 7196345
• 负责人: Mary J Cloninger
• 金额: $ 6.81万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2006-12-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7196345
• 关键词: carbohydrate analog; carbohydrate structure; chemical structure function; chemical synthesis; drug design /synthesis /production; electron spin resonance spectroscopy; intermolecular interaction; polymers

The objective of our research program is to probe key questions in biological chemistry using the tools of the organic chemist. Currently, we seek to understand the protein-carbohydrate interactions that are involved in cell signaling; ultimately, we plan to use this information to formulate multivalent therapeutic agents and vaccines. In this proposal, we describe a novel dendrimer-based system from which artificial multivalent carbohydrate-containing systems will be developed. The techniques we're developing make our system uniquely suited for probing the underlying causes of the multivalent effect in protein- carbohydrate interactions. In addition, the new methods we describe for rapid synthesis of heterogeneously-functionalized dendrimer surfaces are widely applicable. A new method for incorporation of varying concentrations of mannose units onto the surface of G(4)- and G(6)-PAMAM dendrimers is outlined. Evaluation of the interaction of carbohydrate-functionalized dendrimers with lectins using microcalorimetry, hemagglutination, an enzyme-linked lectin assay, and an affinity column/EPR study is proposed. A strategy for EPR characterization of the new dendrimer motifs using TEMPO-labeled dendrimers is also presented.

我们的研究计划的目的是使用有机化学家的工具探讨生物化学中的关键问题。目前，我们试图了解细胞信号传导所涉及的蛋白质碳水化合物相互作用。最终，我们计划使用这些信息来制定多价治疗剂和疫苗。在该提案中，我们描述了一种新型基于树枝状聚合物的系统，将从该系统中开发出人工多价含碳水化合物的系统。我们正在开发的技术使我们的系统非常适合探测蛋白质碳水化合物相互作用多价效应的根本原因。此外，我们描述的新方法是快速合成异质功能的树枝状聚合物表面。概述了一种将不同浓度的甘露糖单元掺入G（4） - 和G（6）-PAMAM树枝状聚合物的新方法。使用微钙化，凝血液，酶联凝集素测定和亲和力柱/EPR研究的碳水化合物官能化树突聚合物与凝集素的相互作用评估。还提出了使用TEMPO标记的树枝状聚合物对新的树枝状聚合物基序进行EPR表征的策略。