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Programable Modular Synthesis of Sulfated N-Glycans and O-Glycans

Award Number: R01GM152688
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: 02/01/2024
PERIOD OF PERFORMANCE END DATE: 11/30/2027

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Programable Modular Synthesis of Sulfated N-Glycans and O-Glycans - Project Summary Sulfation is the most abundant and diverse glycan modification which tunes the physical properties and biological activity of residing glycans and glycoproteins. Other than sulfated glycosaminoglycans (GAGs), sulfation is also commonly identified on N-glycans and O-glycans but is often overlooked. These glycans are believed to play critical roles in many physiological/pathological processes and glycan-protein interactions, the first example of which was the discovery of sulfated glycan ligand (on both N-glycans and O-glycans) for L- selectin in lymphocyte homing and recruitment. Many Siglec-glycan ligand interactions are also found to be “sulfation dependent” or enhance by sulfation. Nevertheless, current knowledge of the structures and functions of these sulfated glycans is still limited, and mainly concluded from genetic studies and the use of simple sulfated glycan determinants, which may not be complete or accurate as underlying structures significantly affect glycan- protein interactions. Despite the significance, systematic synthesis of sulfated N-glycans and O-glycans has never been achieved, which represents a major obstacle in understanding glycan sulfation. A major challenge is the great diversity which is derived from multiple branches and cores of N-glycans and O-glycans, as well as many potential locations of sulfate groups on them. The presence of keratan sulfate chains on N-glycans and O- glycans further expands the sulfated glycan repository. To completely solve this problem, we propose to develop a chemoenzymatic modular synthesis platform, by integrating sulfation modules into our current modular synthesis platform for non-sulfated N-glycans and O-glycans. Mammalian sulfotransferases will be expressed, fully characterized in terms of activity and acceptor specificity, and used to construct efficient sulfation modules. Optimized sulfation modules will then be combined with glycosylation modules to synthesize sulfated structures. The modular synthetic process will be well-programmed based on the substrate specificity of involved enzymes. A comprehensive library (300+) of sulfated N-glycan, O-glycan, and keratan sulfates will be prepared to showcase the powerfulness of the modular synthesis platform. Multiple chemical or enzymatic modulations will be introduced to achieve regio- and branch-selective sulfation. The resulting compounds are important standards for glycomics analysis and probes to understand the functions of sulfated glycans as well as many biological processes. The modular synthesis process is programmable and can be readily adopted for automated synthesis.


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 = $294,840 )
2026	2026	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Biomedical Research and Research Training	000	3	12/15/2025	NON-COMPETING CONTINUATION	$294,840
														Subtotal = $294,840

Issue Date FY: 2025 ( Subtotal = $327,600 )
2025	2025	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Biomedical Research and Research Training	000	2	10/31/2024	NON-COMPETING CONTINUATION	$294,840
2025	2025	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Biomedical Research and Research Training	001	2	8/6/2025	NON-COMPETING CONTINUATION	$32,760
														Subtotal = $327,600

Issue Date FY: 2024 ( Subtotal = $327,600 )
2024	2024	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Biomedical Research and Research Training	000	1	1/15/2024	NEW	$327,600
														Subtotal = $327,600

Grand Total All Awards = $950,040

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Programable Modular Synthesis of Sulfated N-Glycans and O-Glycans

Award Number: R01GM152688

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: 02/01/2024

PERIOD OF PERFORMANCE END DATE: 11/30/2027

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