New Amphiphilic Dendrimers for Encapsulation and Release

 描述（由申请人提供）：该提案描述了在水性环境中基于多功能两亲性树枝状聚合物的超分子组装体的设计和开发，其响应于作为刺激的特定蛋白质而分解。在刺激敏感的超分子组装方面已经取得了很大的进展;然而，这些主要集中在对诸如pH、温度或氧化还原条件等因素的变化做出反应的系统上，这些因素是生物学中的次级不平衡。生物失衡的最直接和最主要的指标涉及蛋白质活性的变化。因此，产生响应蛋白质的超分子组装体是令人兴奋的。我们的主要目标是获得更好的理解的结构因素，控制响应于特定蛋白质的浓度或酶的活性的组装/拆卸事件。实现对这些组装/拆卸事件的控制的结构要求是相当严格的。该提案描述了第一个协调一致的方法，以实现基于树枝状聚合物的两亲性组件响应于特定的蛋白质刺激的受控拆卸，以了解这些结构要求。我们采用三种互补的方法通过与蛋白质的相互作用来分解树枝状聚合物组装体：（i）其中蛋白质非共价结合到树枝状聚合物中的特定配体官能团;（ii）其中蛋白质诱导树枝状聚合物的官能团的共价修饰;（iii）其中蛋白质诱导树枝状聚合物的官能团的共价修饰。以及（iii）其中具有相反官能团转化能力的两种酶使得超分子组装体仅在存在下才做功生物能源。拟议的研究将导致一种新的，蛋白质响应的超分子平台，在几个生物医学应用的影响。

 DESCRIPTION (provided by applicant): This proposal describes the design and development of versatile amphiphilic dendrimer-based supramolecular assemblies, in aqueous milieu, that disassemble in response to specific proteins as stimuli. There have been great advances in stimuli-sensitive supramolecular assemblies; however, these have primarily focused on systems that respond to changes in factors such as pH, temperature, or redox conditions, which are secondary imbalances in biology. The most direct and primary indicator of imbalance in biology involves change in protein activity. Therefore, generating supramolecular assemblies that respond to proteins is exciting. Our primary objective is to obtain a better understanding of the structural factors that control the assembly/disassembly events in response to the concentration of a specific protein or activity of an enzyme. The structural requirements for achieving control over these assembly/disassembly events are quite stringent. This proposal describes the first, concerted approach to achieve controlled disassembly of dendrimer-based amphiphilic assemblies in response to a specific protein stimulus, in order to understand those structural requirements. We take three complementary approaches to disassemble the dendrimer assemblies through interaction with proteins: (i) where the protein non-covalently binds to specific ligand functionalities in the dendrimer; (ii) where the proteins induce a covalent modification of the functionalities of the dendrimers; and (iii) where two enzymes with opposing functional group transformation capabilities render the supramolecular assemblies perform work only in the presence of a biological energy source. The proposed research will result in a novel, protein- responsive supramolecular platform with implications in several biomedical applications.