- ?Chemical Tools for the Investigation and Manipulation of Protein Glycosylation? The broad goal of this proposal is the development of chemical tools that will enable the facile and robust identification of glycoproteins, inhibition of specific types of glycosylation, and the discovery of glycosylation- mediated biological interactions. The addition of carbohydrates to proteins, or glycosylation, is one of the most common forms of posttranslational modifications and is associated with various processes, including protein stability, macromolecular interactions, and cellular signaling. Unfortunately, the currently available tools for interrogating these functions fall short, which limits the study of glycosylation to a few expert labs. We plan to tackle this unmet need in three specific aims.
Aim 1 builds on our development of metabolic chemical reporters, with a focus on making these chemical tools selective for different classes of glycosylation.
Aim 2 proposes to directly transform selective chemical reporters into selective small-molecule inhibitors of specific glycosyltransferases.
Aim 3 leverages the advantages of chemoenzymatic modification of glycosylation to install specific photo-cross-linkers onto living cells, with a focus on identifying biological interactions that are mediated by glycans.

Public Health Relevance

- ?Chemical Tools for the Investigation and Manipulation of Protein Glycosylation? Glycoproteins represent a large fraction human proteins that become modified by carbohydrates. The structure and levels of these carbohydrates often change in diseases. However, the exact nature of these changes and how they affect the underlying biology of diseased cells are extremely difficult to determine with existing technologies. The goal of this project is to create new, facile tools that can be used by the broad scientific community where they can be applied to a range of biomedical investigations in the future.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM125939-03
Application #
9695984
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Bond, Michelle Rueffer
Project Start
2017-09-15
Project End
2022-05-31
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Southern California
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089