new biomarker for citrullination (myelin degeneration)

[frodo]

New Chemical Probes for Detection of Molecular Markers of Multiple Sclerosis

https://faseb.onlinelibrary.wiley.com/d ... 4.s1.06850

Abstract

Multiple sclerosis is a neurodegenerative disease of central nervous system characterized by an autoimmune response against the myelin sheath. The causes and mechanism of the development of the pathology are still not fully understood, but one of the main molecular markers of the disease development appear to be an extensive citrullination of a myelin basic protein.

Citrullination is a post‐translational modification, specifically a deimination, of a side chain of an amino acid arginine, which results in significant changes in protein structure. Therefore, reliable detection of this modification would be indispensable for the study and diagnosis of the disease.

However, detection of this post‐translational modification by mass‐spectrometry is difficult due to a small change in mass of the amino acid and as a result, small molecule chemical probes emerged as a tool of choice for citrulline detection. While several probes have been reported, the field is still in its infancy and novel more potent and more efficacious probes are required.

Our group has been engaged in the development of modular chemical probes for detection of citrulline. In such probes a reactive head that labels citrulline and a detection tag that allows visualization of labeled citrulline are synthesized and administered separately.

Here we present design and synthesis of the chemical probes using 1,3‐dicarbonyl molecules as the reactive heads for the labeling of citrulline. To demonstrate the utility of these probes their reactivity with model compounds, such as N‐ethylurea , N,N‐diethylcitrullinamide, and a citrulline‐containing peptide have also been investigated and the results will be discussed.