Bioorganic and Biomaterials chemistry: Increasing the stability of carbohydrates, decreasing the stability of peptides

这项提议使用了合成化学的工具，并将其应用于制造碳水化合物和氨基酸的人工版本，这是生命的两个主要组成部分。这项提议特别关注制造可能被证明有用的新型碳水化合物分子作为抗癌疫苗，并使用氨基酸作为核心结构，开发可以在命令下降解的新型智能材料。 癌症目前正在使用侵略性技术进行治疗。另一种选择是使用免疫系统来攻击癌症。许多癌症的表面有健康细胞所没有的特殊糖类。如果能告诉免疫系统针对这些糖类并杀死这些细胞，那么癌症就可以被摧毁。疫苗的设计就是为了做到这一点，但当使用糖时，免疫系统无法做出反应。这主要归因于两个因素：糖类不会很好地刺激免疫系统，糖类在体内持续时间不会很长，在启动全面免疫反应之前可能会被破坏。对于提议的计划的第一个目标，我的研究实验室将生产不容易分解的人造糖，作为一种新的抗癌疫苗。然而，由于这些人造糖的制造具有挑战性，而且在自然界中不存在，我们正在开发一系列新的化学反应，以快速且廉价地制造它们。由于在许多更致命的癌症中发现了这些相同的糖，这项研究可以帮助开发未来的癌症治疗方法。 拟议计划的第二个目标是制造智能可降解聚合物。这些塑料可以在几个小时或几天的时间内被降解。启动这一过程的信号可以是几乎任何刺激，从光到热、酸度、酶或特定的化学物质。许多最有希望的应用将在医学上，而这些用途需要一种无毒的分子。我的研究团队正在用氨基酸制造这些塑料，氨基酸是生命的基本组成部分之一。我们还想用同样的方法来制造新型的纳米中空管，这些空管可以用于医药，或者用作纳米反应器，或者作为分子机器的基础。分子机器获得了2016年诺贝尔奖，我们希望利用我们的可降解聚合物为这一领域做出贡献，为生物医学、工业和消费市场创造新的智能材料。 这笔资金将支持寻找新的方法来制造非天然碳水化合物和氨基酸，这些碳水化合物和氨基酸可以做天然碳水化合物做不到的事情，因为它们有不同的形状，或者只是更稳定。这项研究将推进生物化学和材料科学的基础领域；未来它可能被应用于开发癌症治疗方法和制造新型靶向给药装置，从而显着减少化疗的有害副作用。

This proposal uses the tools of synthetic chemistry and applies them to making artificial versions of carbohydrates and amino acids, two of the primary building blocks of life. This proposal is specifically focused on making new types of carbohydrate molecules that may prove useful as anti-cancer vaccines, and using amino acids as the core structure for developing new classes of smart materials that can degrade on command. Cancer is currently treated using aggressive techniques. An alternative would be to use the immune system to attack the cancer. Many cancers have special sugars on their surface that are not found on healthy cells. If the immune system can be taught to target these sugars and kill those cells, then the cancer can be destroyed. Vaccines are designed to do this, but when sugars are used, the immune system fails to respond. This is due to two main factors: sugars do not excite the immune system very well, and sugars do not last very long in the body and can be destroyed before they can initiate a full immune response. For the first aim of the proposed program, my research lab will make artificial sugars that cannot be easily broken down as a new class of anti-cancer vaccines. However, as these artificial sugars are challenging to make and do not exist in nature, we are developing a series of new chemical reactions to make them quickly and inexpensively. As these same sugars are found in many of the deadlier cancers, this research can help in the development of future cancer cures. The second aim of the proposed program involves making smart degradable polymers. These are plastics that can be degraded on command over a few hours or days. The signal to start this process can be almost any stimulus, from light, to heat, acidity, enzymes, or specific chemicals. Many of the most promising applications would be in medicine, and for these uses a non-toxic molecule is needed. My research team is making these plastics out of amino acids which are one of the basic building blocks of life. We also want to use this same approach to make new types of nanoscale hollow tubes that could be used for medicine or as nano-reactors or as the basis of molecular machines. Molecular machines won the 2016 Nobel Prize, and we are looking to contribute to this field using our degradable polymers to create new smart materials for biomedicine, industry and the consumer market. This funding will support finding new ways to make unnatural carbohydrates and amino acids that can do things the natural ones can't because they have different shapes or are just much more stable. This research will advance the fundamental fields of both biological chemistry and materials science; in the future it could be applied to developing cancer treatments and making new types of targeted drug delivery devices that would significantly decrease the harmful side-effects from chemotherapy.