Synthesis and hyperpolarisation of eNOS substrates for quantification of NO production by (1)H NMR spectroscopy.
 

Synthesis and hyperpolarisation of eNOS substrates for quantification of NO production by (1)H NMR spectroscopy.

http://www.bionmr.com//www.ncbi.nlm....PubMedLink.gif http://www.bionmr.com//www.ncbi.nlm....elsevieroa.png Related Articles Synthesis and hyperpolarisation of eNOS substrates for quantification of NO production by (1)H NMR spectroscopy.

Bioorg Med Chem. 2017 May 15;25(10):2730-2742

Authors: Fernandez Diaz-Rullo F, Zamberlan F, Mewis RE, Fekete M, Broche L, Cheyne LA, Dall'Angelo S, Duckett SB, Dawson D, Zanda M

Abstract
Hyperpolarization enhances the intensity of the NMR signals of a molecule, whose in vivo metabolic fate can be monitored by MRI with higher sensitivity. SABRE is a hyperpolarization technique that could potentially be used to image nitric oxide (NO) production in vivo. This would be very important, because NO dysregulation is involved in several pathologies, including cardiovascular ones. The nitric oxide synthase (NOS) pathway leads to NO production via conversion of l-arginine into l-citrulline. NO is a free radical gas with a short half-life in vivo (?5s), therefore direct NO quantification is challenging. An indirect method - based on quantifying conversion of an l-Arg- to l-Cit-derivative by (1)H NMR spectroscopy - is herein proposed. A small library of pyridyl containing l-Arg derivatives was designed and synthesised. In vitro tests showed that compounds 4a-j and 11a-c were better or equivalent substrates for the eNOS enzyme (NO2(-) production=19-46?M) than native l-Arg (NO2(-) production=25?M). Enzymatic conversion of l-Arg to l-Cit derivatives could be monitored by (1)H NMR. The maximum hyperpolarization achieved by SABRE reached 870-fold NMR signal enhancement, which opens up exciting future perspectives of using these molecules as hyperpolarized MRI tracers in vivo.


PMID: 28365086 [PubMed - indexed for MEDLINE]



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