Adaptive Artificial Receptors for Biomimetic Functions

仿生功能的自适应人工受体

• 批准号: MR/S035486/2
• 负责人: Sarah Pike
• 金额: $ 68.85万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS035486%2F2
• 关键词: Adaptive; Artificial; Receptors; Biomimetic; Functions

Over the past few decades, chemists have developed very efficient methods for making molecular containers from simple building blocks. These molecular containers are of great interest as chemists have shown that the hollow cavity within their centre can be used to capture a wide range of guest molecules on the inside the container. Chemists often choose to capture guest molecules with biological relevance as these systems then have the potential to then be used for medical applications; for example to treat diseases within our bodies, e.g. for capturing anticancer drug molecules with long-term potential uses in the treatment of cancer or for the sensing of sugar molecules which holds potential applications in diagnosing and management of diabetes. However, one of the major drawbacks of many existing molecular containers is that because they are made from rigid artificial building blocks, these inflexible molecular containers are unable to display responsive behaviour. As a result, the rigid molecules containers, unlike biological systems, are not able to adapt to the changes in environment and, instead of being able to treat a disease at a specific site within our bodies, they will interact with different molecules within our bodies and lose their ability to effectively treat the disease at its source. Therefore, in order to make full use of the potential of these molecular containers for medical applications within our bodies (for example sugar sensing and anticancer treatments) we need to make sure that they can interact with only the desired guest molecule (be that a sugar or drug molecule) and not with all the other undesired components and molecules within our bodies. The proposed research addresses this problem associated with existing rigid molecular containers and describes the development of a new type of molecular container that uses flexible building blocks made from biologically inspired components. These new molecular containers have specific sites incorporated into their central cavity which allows them to be able to selectively interact with the one desired guest molecule from a large mixture of guest molecules. The ability of these flexible molecular containers to selectively interact with one molecule in a complex mixture of molecules is inspired by the "lock-and-key" mechanisms used by many biological systems. Moreover, the flexible nature of the biologically inspired building blocks also allows these new molecular containers to undergo controlled changes in their shape so that they can completely break apart in order to release the guest molecule from the central cavity in a controlled manner when desired. This responsive behaviour of the molecular container, for the controlled capture and release of one specific and desired guest molecule (for example an anti-cancer drug molecule) even in the presence of large numbers of other undesired guest molecules, means that they have the potential to adapt to the complicated environments found within our bodies. As a result of this responsive behaviour, these new flexible molecular containers have the potential to be used for biomedical applications e.g. capturing an anticancer drug molecule, transporting it to the site of tumour within our bodies and then releasing the anticancer drug at the tumour site in order to treat the disease in a more efficient manner than current anti-cancer treatments. The development of these new molecular containers, which contain flexible biological building blocks, that are able to adapt to interact with one desired guest molecule from a complex mixture, have a clear advantage over many existing ones as they have the striking potential to carry out medical applications within our bodies, for example the sensing of a sugar molecule or deliver an anticancer drug to a tumour site.

在过去的几十年里，化学家们已经开发出非常有效的方法，可以用简单的积木来制造分子容器。这些分子容器引起了人们的极大兴趣，因为化学家们已经证明，它们中心的空腔可以用来捕获容器内部的各种客体分子。化学家通常选择捕获具有生物相关性的客体分子，因为这些系统然后有可能被用于医疗应用；例如，用于治疗我们体内的疾病，例如用于捕获在癌症治疗中具有长期潜在用途的抗癌药物分子，或者用于感测在糖尿病诊断和治疗中具有潜在应用的糖分子。然而，许多现有分子容器的一大缺点是，由于它们是由刚性的人造积木制成的，这些僵硬的分子容器无法表现出响应行为。因此，与生物系统不同的是，刚性分子容器不能适应环境的变化，不能在我们体内的特定位置治疗疾病，而是会与我们体内的不同分子相互作用，失去从源头上有效治疗疾病的能力。因此，为了充分利用这些分子容器在我们体内的医疗应用(例如糖感和抗癌治疗)的潜力，我们需要确保它们只能与所需的客体分子(无论是糖或药物分子)相互作用，而不是与我们体内所有其他不需要的成分和分子相互作用。这项拟议的研究解决了与现有刚性分子容器相关的问题，并描述了一种新型分子容器的开发，这种新型分子容器使用由生物启发的组件制成的柔性积木。这些新的分子容器将特定的位置合并到它们的中央空腔中，使它们能够从大量的客体分子混合物中选择性地与一个所需的客体分子相互作用。这些灵活的分子容器能够选择性地与复杂的分子混合物中的一个分子相互作用的能力，是受到许多生物系统使用的“锁和钥匙”机制的启发。此外，生物灵感构建块的柔性性质还允许这些新的分子容器在形状上进行受控变化，以便它们可以完全分离，以便在需要时以受控的方式将客体分子从中心空腔中释放出来。分子容器的这种响应行为，即使在大量其他不受欢迎的客体分子存在的情况下，也能控制捕获和释放一个特定和所需的客体分子(例如抗癌药物分子)，这意味着它们有可能适应我们体内的复杂环境。由于这种响应行为，这些新的柔性分子容器有可能被用于生物医学应用，例如捕获抗癌药物分子，将其输送到我们体内的肿瘤部位，然后在肿瘤部位释放抗癌药物，以便以比目前抗癌治疗更有效的方式治疗疾病。这些新的分子容器包含灵活的生物构建块，能够适应与复杂混合物中的一个期望的客体分子相互作用，与许多现有的分子容器相比，它们的开发具有明显的优势，因为它们具有在我们体内进行医疗应用的惊人潜力，例如感测糖分子或将抗癌药物输送到肿瘤部位。

项目成果

Reversible conformational switching of a photo-responsive ortho-azobenzene/2,6-pyridyldicarboxamide heterofoldamer.

光响应性邻偶氮苯/2,6-吡啶二甲酰胺杂折叠体的可逆构象转换。

• DOI: 10.1039/d3ob01137b
• 发表时间: 2023
• 期刊: Organic & biomolecular chemistry
• 影响因子: 3.2
• 作者: Pike SJ

Influence of Terminal Functionality on the Crystal Packing Behaviour and Cytotoxicity of Aromatic Oligoamides.

• DOI: 10.3389/fchem.2021.709161
• 发表时间: 2021
• 期刊: Frontiers in chemistry
• 影响因子: 5.5
• 作者: Delfosse P;Seaton CC;Male L;Lord RM;Pike SJ
• 通讯作者: Pike SJ

Influence of Ligand and Nuclearity on the Cytotoxicity of Cyclometallated C^N^C Platinum(II) Complexes.

• DOI: 10.1002/chem.202002517
• 发表时间: 2020-11-20
• 期刊: Chemistry (Weinheim an der Bergstrasse, Germany)
• 作者: Kergreis A;Lord RM;Pike SJ
• 通讯作者: Pike SJ