New Amphiphilic Dendrimers for Encapsulation and Release

 描述(由申请人提供)：本提案描述了在水环境中设计和开发多功能两亲性树枝状大分子超分子组装体，该组装体在特定蛋白质的刺激下分解。在对刺激敏感的超分子组装方面已经有了很大的进展；然而，这些进展主要集中在对诸如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要失衡。生物不平衡的最直接和最主要的指标涉及蛋白质活性的变化。因此，产生对蛋白质有反应的超分子组装是令人兴奋的。我们的主要目标是更好地了解控制组装/拆卸事件的结构因素，以响应特定蛋白质的浓度或酶的活性。实现对这些组装/拆卸事件的控制的结构要求相当严格。这项建议描述了第一种协调一致的方法，以实现对树枝状大分子两亲性组件的受控拆解，以响应特定的蛋白质刺激，以了解这些结构要求。我们采取了三种互补的方法通过与蛋白质的相互作用来拆解树枝状大分子组装：(I)蛋白质非共价结合树状大分子中的特定配体功能；(Ii)蛋白质诱导树枝状大分子功能的共价修饰；以及(Iii)两种具有相反官能团转化能力的酶使超分子组装仅在生物能源存在的情况下执行工作。这项拟议的研究将产生一种新颖的、蛋白质响应的超分子平台，并将在几个生物医学应用中发挥作用。

 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.