Heparin–polynitroxides: Synthesis and preliminary evaluation as cardiovascular EPR/MR imaging probes and extracellular space-targeted antioxidants
We report here the synthesis of heparin-polynitroxide derivatives (HPNs) in which nitroxide moieties are linked either to uronic acid or glycosamine residues of the heparin macromolecule. HPNs have low anticoagulant activity, possess superoxide scavenging properties, bind to the vascular endothelium/extra-cellular matrix and can be detected by EPR and MRI techniques. As the vascular wall-targeted redox-active paramagnetic compounds, HPNs may have both diagnostic (molecular MRI) and therapeutic (ecSOD mimics) applications.
Heparin–polynitroxide derivatives: a platform for new diagnostic and therapeutic agents in cardiovascular disease?
Vascular wall extracellular oxidative stress Cardiovascular disease (CVD; mainly atherosclerosis, hypertension and diabetes mellitus) remains a major cause of death in western society [1]. Despite substantial progress achieved, the diagnosis of CVD often comes too late, when the disease has already advanced to therapeutically incurable stages. The development of efficient diagnostic probes allowing early non-invasive diagnostics, as well as drugs which can prevent or reverse CVD and/or its complications (e.g., myocardium infarctus and stroke) are highly desired tasks of the modern cardiovascular medicinal chemistry.
Spin‐Labeled Heparins as Polarizing Agents for Dynamic Nuclear Polarization
A potentially biocompatible class of spin-labeled macromolecules, spin-labeled (SL) heparins, and their use as nuclear magnetic resonance (NMR) signal enhancers are introduced. The signal enhancement is achieved through Overhauser-type dynamic nuclear polarization (DNP). All presented SL-heparins show high 1 H DNP enhancement factors up to E=-110, which validates that effectively more than one hyperfine line can be saturated even for spin-labeled polarizing agents. The parameters for the Overhauser-type DNP are determined and discussed. A striking result is that for spin-labeled heparins, the off-resonant electron paramagnetic resonance (EPR) hyperfine lines contribute a non-negligible part…