Molecular self-assembly of amino acid pairing peptides and their derivatives

分子自组装一直是纳米技术研究的标志，在各种工程和生物医学过程中的应用。我们已经开发了一类新的自组装生物分子：氨基酸配对（AAP）肽。就像DNA双螺旋中的碱基配对一样，氨基酸配对允许肽分子的自组装，从而产生所需的功能性纳米结构。AAP肽不仅具有特定的分子功能（例如，刺激响应性、微环境识别和细胞膜靶向），而且还从其用于分子自组装/共组装的独特氨基酸序列获得表面活性剂样或两亲性特征。这些肽及其组装的纳米结构或纳米载体能够与其他分子相互作用，例如，如抗癌药物中的疏水性化合物，如DNA和siRNA（短干扰RNA）中的亲水性分子，以及不同的工程表面。它们被发现在药物和基因递送中是有用的。在这个提案中，我们建议扩大我们的研究肽自/共组装和纳米车辆的设计。 我们的短期目标是：*（1）探索氨基酸配对肽及其衍生物的分子设计和纳米结构形成;*（2）评估设计的氨基酸配对肽及其自组装纳米载体的刺激响应性或微环境识别;*（3）阐明肽和细胞膜的相互作用，其中自组装纳米结构及其对细胞膜独特表面性质的响应将被揭示;* （4）研究肽和石墨烯或其衍生物的相互作用/杂交，其中分子细节将在肽-石墨烯络合上揭示，以实现石墨剥离和氧化石墨烯衍生物的功能化。*我们的长期目标是：*（1）在该领域首次建立一系列分子工程工具，通过氨基酸配对原理设计肽的一级、二级、三级和纳米结构;*（2）通过肽氨基酸配对或肽残基与共组装分子的官能团/部分之间的配对构建新型纳米载体，其中最大分子负载、刺激响应性、靶向和控制释放都可以实现。*这些多功能分子机器或纳米车辆将在生物医学工程中得到广泛的应用，包括生物传感器，表面改性以及靶向药物和基因递送。我们计划在项目结束时成立一家分拆公司，将开发的技术商业化。受训学生可能会参与这项奋进，但他们将熟练掌握许多其他高科技工作，特别是在纳米技术，化学分子设计和纳米医学，所有这些都对未来的加拿大经济至关重要。

Molecular self-assembly has been the hallmark of nanotechnology research, with applications in various engineering and biomedical processes. We have developed a new class of self-assembling biomolecules: amino acid pairing (AAP) peptides. Just like the base pairing in a DNA double helix, amino acid pairing allows self-assembly of peptide molecules, leading to desired functional nanostructures. The AAP peptides not only possess specific molecular functions (e.g., stimuli-responsiveness, micro-environment recognition, and cell membrane targeting) but also derive surfactant-like or amphiphilic characteristics from their unique amino acid sequences for molecular self/co-assembly. These peptides and their assembled nanostructures, or nano-vehicles, are able to interact with other molecules, e.g., hydrophobic compounds as in anticancer drugs, hydrophilic molecules as in DNAs and siRNAs (short interfering RNAs), and different engineering surfaces. They have been found to be useful in drug and gene delivery.*******In this proposal, we propose to expand our research on peptide self/co-assembly and nano-vehicle design. Our short term objectives are to:*******(1) explore molecular design and nano-structure formation of amino acid pairing peptides and their derivatives;****(2) evaluate stimuli-responsiveness or micro-environment recognition of designed amino acid pairing peptides and their self-assembled nano-vehicles;****(3) elucidate peptide and cell membrane interaction, where self-assembled nanostructures and their responses to the unique surface properties of cell membranes will be uncovered;****(4) investigate interaction/hybridization of peptide and graphene or their derivatives, where molecular details will be revealed on the peptide-graphene complexation, to achieve graphite exfoliation and functionalization of graphene oxide derivatives.*******Our long term objectives are to:****(1) establish a cluster of molecular engineering tools, the first time in the field, to design peptide primary, secondary, tertiary and nano-structures via the amino acid pairing principle;****(2) construct novel nano-vehicles via peptide amino acid pairing or pairing between peptide residues and functional groups/moieties of co-assembled molecules, where maximum molecular cargo loading, stimuli-responsiveness, targeted and controlled release can all be achieved.*******These multi-functional molecular machines or nano-vehicles will find a wide range of biomedical engineering applications, including biosensors, surface modification, and targeted drug and gene delivery. We plan to start a spin-off company at the end of the project to commercialize developed technologies. The student trainees may be involved in this endeavor, but they will be skilled for many other high tech jobs, especially in nanotechnology, chemical molecular design and nanomedicine, all critical to the future Canadian economy.***