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8 August 2019

Design of New Probes for Oxidized Amino Acids Localization †

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1
Aix Marseille Université, CNRS UMR 7273, Institue de Chimie Radicalaire, Equipe Sonde Moléculaires en Biologie et Stress Oxydant, 13013 Marseille, France
2
CRCM, Inserm, 13009 Marseille, France
*
Authors to whom correspondence should be addressed.
Presented at the 2nd Molecules Medicinal Chemistry Symposium (MMCS): Facing Novel Challenges in Drug Discovery, Barcelona, Spain, 15–17 May 2019.
This article belongs to the Proceedings The 2nd Molecules Medicinal Chemistry Symposium (MMCS): Facing Novel Challenges in Drug Discovery
Protein carbonyls (PC) are oxidative damage observed in many diseases. Proteins are possibly the most immediate vehicle for inflicting oxidative damage on cells because they are often catalysts [1]. A fluorometric and UV-absorption method have been developed to quantify PC in blood and tissues samples by labeling with two hydrazines: 7-hydrazino-4-nitrobenzo-2,1,3-oxadiazole (NBDH) and dinitrophenylhydrazine (DNPH), respectively [2,3]. These methods are based on the selective hydrazone formation between the carbonyls group of oxidized protein to yield a strong fluorescent/UV-absorption adduct that is then quantified.
Here, we will describe our study on NBDH’s and DNPH’s derivatives to generate new PC-probes bearing an alkyne moiety. In a first step, the hydrazine moiety reacted specifically with protein carbonyls and in a second step, a click reaction was performed between the alkyne moiety and a cleavable resin [4] to yield a PC’s enrichment. Theses probes have been explored on oxidized bovine serum albumin (OxBSA) for PC-labeling, and the possible sites of oxidation of isolated labelled PC will be studied by LC-MS and proteomics experiments.

References

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