Development and characterization of novel nitric oxide-releasing probes for magnetic resonance imaging

• Main Author: Czerniewski, Alexandre Adam.
• Format: Others
• Language: en
• Published: McGill University 2007
• Subjects: Molecular probes.; Azo compounds.; Beta-galactosidase.; Magnetic resonance imaging.; Molecular Probes.; Azo Compounds.; beta-Galactosidase.; Magnetic Resonance Imaging.
• Online Access: http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112393

While providing non-invasive tissue detection, magnetic resonance imaging (MRI) presently possesses limited sensitivity for protein target recognition. This limitation was addressed for the target beta-galactosidase (beta-gal) by constructing three beta-gal-specific MRI probes. The probes are based on a bipartite design in which a vasoactive moiety known as a diazeniumdiolate (NONOate) is bound to a specifier, specifically galactose. Upon galactose' interaction with beta-gal, the NONOate is cleaved from galactose, and actively generates nitric oxide (NO). The released NO leads to microvascular permeability changes in surrounding tissues affecting localized T1 measurements. These changes serve as a quantitative index of beta-gal detection. The three beta-gal-specific NO-releasing probes constructed include GALPYRNONO, GALPIPNONO and a 'bi-functional' probe, which is similar to the first two but with glucose additionally incorporated so that the third probe may easily cross cellular membranes. Synthesis and characterization of this novel class of MRI probes are described in this work. === Keywords: non-invasive detection, magnetic resonance imaging (MRI), nitric oxide (NO), diazeniumdiolates (NONOates), NO-releasing compounds, novel MRI probes, molecular targets, protein targets, specifier, vasoactive, vasodilation, microvascular permeability, tissue localization, bipartite systems, bifunctional probes, blood-brain barrier, cell membrane trafficking, saccharide-bound NONOates, sugar diazeniumdiolates, glycosylated diazeniumdiolates, galactose, beta-galactosidase, glucose, glucose transporters, thermal & photolytic degradation, half-life optimization, Griess test, rat serum, stability.