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Chemical Tools for Probing Cysteine Sulfenation and Sulfination Redox Biology

Award Number: R01GM102187
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: 08/01/2012
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Chemical Tools for Probing Cysteine Sulfenation and Sulfination Redox Biology - PROJECT SUMMARY Post-translational changes in the redox state of cysteine residues can rapidly and reversibly alter protein function, modulating biological processes and drug pharmacology. During the last funding period, our lab reported several innovations in organosulfur chemistry, small-molecule tools, and computational methods for proteomic analysis that dramatically improved selectivity, cellular application, and site-specific quantitation of the cysteine redoxome (J. Am. Chem. Soc., 2017; Nat. Chem. Biol., 2018; Nat. Chem., 2021; Nat. Comm., 2022). Application of these chemoproteomic methods has contributed to meaningful discovery of new paradigms in redox biology (Nat. Cell Biol., 2019; Cell Metab., 2019; Blood Adv., 2020; Nat. Comm., 2021; Redox Biol., 2021 & 2022; Proc. Natl. Acad. Sci., 2022) and raise interesting new questions about the links between the cellular redox landscape, molecular thiol-based redox switches, and the emerging field of redox medicine. Herein, the following three Specific Aims are proposed: Development and application of 1) chemical methods to address spatiotemporal control in redox signaling; 2) genetic incorporation of oxidized cysteine in proteins to pinpoint molecular mechanisms underlying thiol-based redox regulation; and 3) nucleophile-fragment libraries to discover covalent ligands that target redox- regulated proteins in the cysteinome. Strong preliminary data demonstrate that studies proposed herein are both promising and feasible in our hands. Deliverables resulting from these studies include: 1) valuable new chemical biology approaches to understand fundamental mechanisms in thiol-based redox signaling, and 2) novel chem- ical matter that can be mined as a source of small-molecule probes and as starting points for drug discovery.


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: 2025 ( Subtotal = $242,717 )
2025	2025	FLORIDA ATLANTIC UNIVERSITY	777 GLADES RD	BOCA RATON	FL	33431	PALM BEACH	USA	Biomedical Research and Research Training	002	12	11/7/2024	NON-COMPETING CONTINUATION	$281,363
2025	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	000	10	10/29/2024	NON-COMPETING CONTINUATION	-$183,451
2025	2024	FLORIDA ATLANTIC UNIVERSITY	777 GLADES RD	BOCA RATON	FL	33431	PALM BEACH	USA	Biomedical Research and Research Training	004	11	3/26/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$8,682
2025	2024	FLORIDA ATLANTIC UNIVERSITY	777 GLADES RD	BOCA RATON	FL	33431	PALM BEACH	USA	Biomedical Research and Research Training	001	11	10/30/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$144,805
2025	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	003	10	3/26/2025	NON-COMPETING CONTINUATION	-$8,682
														Subtotal = $242,717

Issue Date FY: 2024 ( Subtotal = $396,060 )
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	001	10	6/5/2024	NON-COMPETING CONTINUATION	$39,605
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	000	10	11/1/2023	NON-COMPETING CONTINUATION	$356,455
														Subtotal = $396,060

Issue Date FY: 2023 ( Subtotal = $396,060 )
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	001	9	2/28/2023	COMPETING CONTINUATION	$396,060
2023	2020	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Biomedical Research and Research Training	000	8	10/30/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $396,060

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Biomedical Research and Research Training	000	8	6/2/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $380,000 )
2020	2020	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Biomedical Research and Research Training	000	8	6/24/2020	NON-COMPETING CONTINUATION	$380,000
														Subtotal = $380,000

Issue Date FY: 2019 ( Subtotal = $433,696 )
2019	2019	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Biomedical Research and Research Training	000	7	6/14/2019	NON-COMPETING CONTINUATION	$433,696
														Subtotal = $433,696

Issue Date FY: 2018 ( Subtotal = $475,465 )
2018	2018	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Biomedical Research and Research Training	000	6	6/25/2018	NON-COMPETING CONTINUATION	$475,465
														Subtotal = $475,465

Issue Date FY: 2017 ( Subtotal = $411,000 )
2017	2017	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Biomedical Research and Research Training	000	5	6/26/2017	COMPETING CONTINUATION	$411,000
2017	2015	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Biomedical Research and Research Training	001	4	8/31/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $411,000

Issue Date FY: 2015 ( Subtotal = $390,531 )
2015	2015	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	000	4	4/15/2015	NON-COMPETING CONTINUATION	$390,531
														Subtotal = $390,531

Issue Date FY: 2014 ( Subtotal = $390,531 )
2014	2014	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	000	3	4/17/2014	NON-COMPETING CONTINUATION	$390,531
														Subtotal = $390,531

Issue Date FY: 2013 ( Subtotal = $376,863 )
2013	2013	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	001	2	6/21/2013	NON-COMPETING CONTINUATION	$25,383
2013	2013	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	000	2	4/18/2013	NON-COMPETING CONTINUATION	$351,480
														Subtotal = $376,863

Issue Date FY: 2012 ( Subtotal = $398,293 )
2012	2012	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Biomedical Research and Research Training	000	1	7/30/2012	NEW	$398,293
														Subtotal = $398,293

Grand Total All Awards = $4,291,216

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Chemical Tools for Probing Cysteine Sulfenation and Sulfination Redox Biology

Award Number: R01GM102187

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: 08/01/2012

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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