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Chemical Synthesis and Biological Application of Carbohydrates and Glycoconjugates

Award Number: R35GM148266
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Chemical Synthesis and Biological Application of Carbohydrates and Glycoconjugates - ABSTRACT Carbohydrates are ubiquitous and play a vital role in many important biological processes. The development of efficient and selective chemical methods for the synthesis of carbohydrates and glycoconjugates is necessary to understand the specific roles of carbohydrates and for therapeutic development. The most prevalent functionality in carbohydrates is the hydroxyl group. There are two fundamental challenges in carbohydrate synthesis associated with the hydroxyl group: 1) site-selective functionalization of one hydroxyl in the presence of many other seemingly identical hydroxyls, and 2) stereoselective glycosylation. One long-term goal of this program is to develop methods to address these challenges and improve the efficiency and selectivity for carbohydrate synthesis. In the next five years, we will develop methods that can site-selectively functionalize hydroxyl groups, such as acylation, alkylation, and sulfation, in various minimally protected or unprotected glycosides in a predictable and general manner. We will also develop methods that can site-selectively remove protecting groups in carbohydrates. The directing groups that are site-selectively installed in carbohydrates will also allow us to access various types of glycosidic linkages stereoselectively. These transformations can significantly improve the efficiency and selectivity for the synthesis of carbohydrates. The other long-term goal of this program is to prepare carbohydrates and glycocongates with novel biological functions. Certain glycans on glycoproteins can be recognized by lysosome targeting receptors (LTRs), which then transport the glycoproteins to the lysosome for degradation. To take advantage of this natural process, lysosome targeting chimeras were recently reported for the degradation of disease-associated extracellular proteins. These degraders are created by conjugating carbohydrate ligands of LTRs on the cell surface with ligands that can bind to the extracellular protein targets. The receptor-ligand interaction then triggers the internalization of the extracellular proteins through receptor-mediated endocytosis, which further induces the degradation of the endogenous extracellular protein targets in the lysosome. This new strategy complements existing targeted protein degradation methods, which largely focus on intracellular proteins. In the next five years, we will develop a series of carbohydrate-based ligands for LTRs that can be used for the degradation of various extracellular disease associated proteins. During our previous studies, we recognized the enormous potential of transition metal catalysts and chiral organocatalysts in carbohydrate synthesis and the unique utility of glycoconjugates in cell-type selective targeted protein degradation. In the next five years, we will continue developing novel methods for the synthesis of carbohydrates and glycoconjugates, studying their applications in targeted protein degradation, and pioneering new research directions.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $340,684 )
2026	2026	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	4	12/17/2025	NON-COMPETING CONTINUATION	$340,684
														Subtotal = $340,684

Issue Date FY: 2025 ( Subtotal = $493,092 )
2025	2025	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	004	3	9/16/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2025	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	003	3	8/5/2025	NON-COMPETING CONTINUATION	$37,854
2025	2025	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	002	3	12/5/2024	SUPPLEMENT FOR EXPANSION	$114,554
2025	2025	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	001	3	12/4/2024	NON-COMPETING CONTINUATION	$340,684
2025	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	2	11/5/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $493,092

Issue Date FY: 2024 ( Subtotal = $512,597 )
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	002	2	7/29/2024	NON-COMPETING CONTINUATION	$37,854
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	2	12/15/2023	NON-COMPETING CONTINUATION	$340,684
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	003	2	8/8/2024	SUPPLEMENT FOR EXPANSION	$57,277
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	001	2	6/6/2024	SUPPLEMENT FOR EXPANSION	$76,782
														Subtotal = $512,597

Issue Date FY: 2023 ( Subtotal = $378,538 )
2023	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	1	1/19/2023	NEW	$378,538
														Subtotal = $378,538

Grand Total All Awards = $1,724,911

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Chemical Synthesis and Biological Application of Carbohydrates and Glycoconjugates

Award Number: R35GM148266

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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