Human Serum Albumin Labelled with Sterically-Hindered Nitroxides as Potential MRI Contrast Agents

Dobrynin, Sergey A.; Kutseikin, Sergei S.; Morozov, Denis A.; Krumkacheva, Olesya A.; Spitsyna, Anna; Gatilov, Yuri V.; Silnikov, Vladimir N.; Angelovski, Goran; Bowman, Michael K.; Kirilyuk, Igor A.; Chubarov, Alexey S.

doi:10.3390/molecules25071709

Cited by 22 publications

(31 citation statements)

References 75 publications

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“…In this work, the spin labels were attached to Cys-34 which made it impossible to measure the impact of natural modifications of Cys-34 on dimerization of HSA. Attachment of spin labels at other sites in HSA [ 32 ], combined with introduction of disease-related modifications at Cys-34 or other relevant sites would allow future DEER experiments to investigate this fascinating possibility of a more direct involvement of HSA in such diseases.…”

Section: Discussionmentioning

confidence: 99%

Reversible Dimerization of Human Serum Albumin

et al. 2020

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Pulsed Dipolar Spectroscopy (PDS) methods of Electron Paramagnetic Resonance (EPR) were used to detect and characterize reversible non-covalent dimers of Human Serum Albumin (HSA), the most abundant protein in human plasma. The spin labels, MTSL and OX063, were attached to Cys-34 and these chemical modifications of Cys-34 did affect the dimerization of HSA, indicating that other post-translational modifications can modulate dimer formation. At physiologically relevant concentrations, HSA does form weak, non-covalent dimers with a well-defined structure. Dimer formation is readily reversible into monomers. Dimerization is very relevant to the role of HSA in the transport, binding, and other physiological processes.

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Section: Discussionmentioning

confidence: 99%

Reversible Dimerization of Human Serum Albumin

et al. 2020

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“…Both mesylation and the Appel reaction were successfully used in nitroxide chemistry, however, the Appel reaction often gives low to moderate yields of brominated nitroxides [ 17 ], while the yields of OMs derivatives are high [ 18 , 19 , 20 ]. The reactions of (5 R ( S ),6 R ( S ))-6-(hydroxymethyl)-2,2-dimethyl-1-azaspiro[4.4]nonan-1-oxyl ( 1a ) with MsCl/NEt 3 or with PPh 3 -CBr 4 afforded no expected nitroxides 7 .…”

Section: Resultsmentioning

confidence: 99%

The Reactions of 6-(Hydroxymethyl)-2,2-dimethyl-1-azaspiro[4.4]nonanes with Methanesulfonyl Chloride or PPh3-CBr4

et al. 2021

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Activation of a hydroxyl group towards nucleophilic substitution via reaction with methanesulfonyl chloride or PPh3-CBr4 system is a commonly used pathway to various functional derivatives. The reactions of (5R(S),6R(S))-1-X-6-(hydroxymethyl)-2,2-dimethyl- 1-azaspiro[4.4]nonanes 1a–d (Х = O·; H; OBn, OBz) with MsCl/NR3 or PPh3-CBr4 were studied. Depending on substituent X, the reaction afforded hexahydro-1H,6H-cyclopenta[c]pyrrolo[1,2-b]isoxazole (2) (for X = O), a mixture of 2 and octahydrocyclopenta[c]azepines (4–6) (for X = OBn, OBz), or perhydro-cyclopenta[2,3]azeto[1,2-a]pyrrol (3) (for X = H) derivatives. Alkylation of the latter with MeI with subsequent Hofmann elimination afforded 2,3,3-trimethyl-1,2,3,4,5,7,8,8a-octahydrocyclopenta[c]azepine with 56% yield.

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“…In other words, this assemble type contrast agent is working as drug carrier simultaneously, and then, monitoring of the loaded drug from the assembled compound were reported [ 132 ]. Nitroxyl radical labeled contrast agents as protein [ 133 ] and amino-acid type [ 134 ] for achieving simultaneous drug delivery and tumor imaging has been reported. A nitroxyl radical labeled proteolysis probe for OMRI has been also proposed [ 135 ].…”

Section: Applications Of Redox Sensitive Nitroxyl Contrast Agents mentioning

confidence: 99%

Multimodal Functional Imaging for Cancer/Tumor Microenvironments Based on MRI, EPRI, and PET

Matsumoto¹,

Mitchell

Krishna

2021

Molecules

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Radiation therapy is one of the main modalities to treat cancer/tumor. The response to radiation therapy, however, can be influenced by physiological and/or pathological conditions in the target tissues, especially by the low partial oxygen pressure and altered redox status in cancer/tumor tissues. Visualizing such cancer/tumor patho-physiological microenvironment would be a useful not only for planning radiotherapy but also to detect cancer/tumor in an earlier stage. Tumor hypoxia could be sensed by positron emission tomography (PET), electron paramagnetic resonance (EPR) oxygen mapping, and in vivo dynamic nuclear polarization (DNP) MRI. Tissue oxygenation could be visualized on a real-time basis by blood oxygen level dependent (BOLD) and/or tissue oxygen level dependent (TOLD) MRI signal. EPR imaging (EPRI) and/or T1-weighted MRI techniques can visualize tissue redox status non-invasively based on paramagnetic and diamagnetic conversions of nitroxyl radical contrast agent. 13C-DNP MRI can visualize glycometabolism of tumor/cancer tissues. Accurate co-registration of those multimodal images could make mechanisms of drug and/or relation of resulted biological effects clear. A multimodal instrument, such as PET-MRI, may have another possibility to link multiple functions. Functional imaging techniques individually developed to date have been converged on the concept of theranostics.

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Human Serum Albumin Labelled with Sterically-Hindered Nitroxides as Potential MRI Contrast Agents

Cited by 22 publications

References 75 publications

Reversible Dimerization of Human Serum Albumin

Reversible Dimerization of Human Serum Albumin

The Reactions of 6-(Hydroxymethyl)-2,2-dimethyl-1-azaspiro[4.4]nonanes with Methanesulfonyl Chloride or PPh3-CBr4

Multimodal Functional Imaging for Cancer/Tumor Microenvironments Based on MRI, EPRI, and PET

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