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

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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.