Towards Functional Peptide-Based Supramolecular Structures

迈向基于功能性肽的超分子结构

• 批准号: RGPIN-2017-04834
• 负责人: Voyer, Normand
• 金额: $ 2.55万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=711102
• 关键词: Towards; Functional; Peptide; Based; Supramolecular

Towards Functional Peptide-Based Supramolecular Structures Inspired by natural sophisticated proteic systems, our research program aims at developing functional supramolecular structures exploiting polypeptide as molecular framework. For the next grant period, we propose to devote our efforts into four areas: 1. Use artificial ion channels as sensing devices We will pursue our development of crown ether peptide-based ion channels towards sensing devices. Several biological recognition elements will be introduced at the N-terminal position to study and eventually to detect the presence of specific biomarkers and cells. 2. Preparing fluorinated channels and nanopores We will synthesize fluorinated helical peptides and study their self-assembly into novel supramolecular architectures driven by fluorine-fluorine interactions. Such superstructures will create fluor-lined channels and nanopores. We intend to study membrane ion transport properties of those fluorinated channels to understand the structural features essential for ion translocation. 3. Developing antimicrobial peptide nanostructures Towards novel and efficient antimicrobials against resistant bacteria, we have used a de novo approach based on a simple 14 residue peptide. We propose to engineer systematically this model peptide with specific functional groups and to study their antimicrobial activities towards important pathogens. Modifications at terminal positions and in the sequence will be evaluated with respect to their impact on bioactivity. 4. Biomimetic supramolecular catalysis in water To catalyze efficiently industrially relevant organic transformations in water, we propose to synthesize a variety of peptide structures that can acts as supramolecular catalysts, hence mimicking natural enzymes. We will investigate several peptidic systems; from small rigid cyclic peptides, to conformationally biased oligopeptides. Different transformations will be studied as model reactions. Factors influencing efficiency will be identified with the goal of delineating design principles for developing biomimetic catalysts for a huge variety of transformations in water.

走向功能化的多肽超分子结构 受天然复杂蛋白质系统的启发，我们的研究计划旨在利用多肽作为分子骨架来开发功能性超分子结构。在下一个资助期，我们建议致力于以下四个方面： 1.使用人造离子通道作为传感设备 我们将继续开发基于冠醚多肽的离子通道，以用于传感设备。将在N端位置引入几个生物识别元件来研究并最终检测特定生物标志物和细胞的存在。 2.制备含氟通道和纳米孔 我们将合成含氟螺旋多肽，并研究它们在氟-氟相互作用驱动下自组装成新型超分子结构。这样的超结构将产生氟衬里的通道和纳米孔。我们打算研究这些氟化通道的膜离子转运特性，以了解离子转运所必需的结构特征。 3.开发抗菌肽纳米结构 对于新的和有效的抗药性细菌的抗菌药，我们使用了一种基于简单的14个残基的从头开始的方法。我们建议系统地设计这种具有特定功能基团的模型肽，并研究其对重要病原体的抗菌活性。末端位置和序列中的修饰将根据它们对生物活性的影响进行评估。 4.水中的仿生超分子催化 为了有效地催化水中与工业相关的有机转化，我们建议合成各种可以作为超分子催化剂的多肽结构，从而模拟天然酶。我们将研究几个多肽系统；从小的刚性环肽到构象偏向的寡肽。不同的转化将作为模型反应进行研究。将确定影响效率的因素，以描述开发用于水中各种变化的仿生催化剂的设计原则。