A fluoroacetamidine-based inactivator of protein arginine deiminase 4: design, synthesis, and in vitro and in vivo evaluation.

A fluoroacetamidine-based inactivator of protein arginine deiminase 4: design, synthesis, and in vitro and in vivo evaluation. Research Abstract Details 

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A fluoroacetamidine-based inactivator of protein arginine deiminase 4: design, synthesis, and in vitro and in vivo evaluation. Abstract Text:

Yuan Luo,Bryan Knuckley,Young-Ho Lee,Michael R Stallcup,Paul R Thompson,

Protein arginine deiminase 4 (PAD4) is a calcium-dependent transcriptional corepressor that has been implicated in the onset and progression of rheumatoid arthritis. Herein we describe the synthesis and in vitro evaluation of a fluoroacetamidine-containing compound, N-alpha-benzoyl-N5-(2-fluoro-1-iminoethyl)-l-ornithine amide, 1, hereafter referred to as F-amidine, that is the most potent PAD4 inhibitor ever described. Additional studies described herein indicate that F-amidine can also inhibit PAD4 activity in vivo. The bioavailability of this compound suggests that F-amidine will be a powerful chemical probe of PAD4 function that can be used to dissect the roles of this enzyme in both rheumatoid arthritis and transcriptional control. The fact that inhibition is of an irreversible nature suggests that, with appropriate functionalization, F-amidine analogues will be robust activity-based protein-profiling and proteomic capture reagents.

A fluoroacetamidine-based inactivator of protein arginine deiminase 4: design, synthesis, and in vitro and in vivo evaluation. Publishing Authors By Initials

Y Luo,B Knuckley,YH Lee,MR Stallcup,PR Thompson,

For similar chemical and pharmacologic phenomena: kinetics research abstracts see: chemical and pharmacologic phenomena: kinetics research

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A fluoroacetamidine-based inactivator of protein arginine deiminase 4: design, synthesis, and in vitro and in vivo evaluation. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of the American Chemical Society

VOLUME: 128

Page Numbers: 1092-3

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 1

MONTH: Feb

YEAR: 2006

A fluoroacetamidine-based inactivator of protein arginine deiminase 4: design, synthesis, and in vitro and in vivo evaluation. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7503056

A fluoroacetamidine-based inactivator of protein arginine deiminase 4: design, synthesis, and in vitro and in vivo evaluation. Keywords Mesh Terms:

KEYWORDS: Kinetics

MESH TERMS: metabolism

Chemical & Substance for Abstract: A fluoroacetamidine-based inactivator of protein arginine deiminase 4: design, synthesis, and in vitro and in vivo evaluation. Information

Substance Name: peptidylarginine deiminase type IV

Registry Number: EC 3.5.3.15

Grant and Affiliation Information for A fluoroacetamidine-based inactivator of protein arginine deiminase 4: design, synthesis, and in vitro and in vivo evaluation.

AFFILIATION: Department of Chemistry & Biochemistry, University of South Carolina, Columbia, 29208, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: R01 DK055274-08

ACRONYM: DK

MEDLINETA: J Am Chem Soc

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