Document Detail


Redox-active magnetic resonance imaging contrast agents: studies with thiol-bearing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid derivatives.
MedLine Citation:
PMID:  23148501     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The synthesis and structure-activity relationships of a homologous series of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid gadolinium(III) complexes bearing thiol-terminated alkyl side chains from three to nine carbons in length are reported. The observed binding with human serum albumin (HSA) of the compounds having C-3 through C-7 side chain lengths was inhibited by homocysteine in a manner consistent with single-site binding. The observed binding with HSA of the compounds having C-8 and C-9 side chain lengths was only partly inhibited by homocysteine, consistent with multisite binding. The binding affinity of the C-7 compound could be related to the HSA oxidation state. 2D 1H-1H NMR TOCSY provided evidence of covalent binding of the europium analog of the C-6 compound to HSA-Cys34. The longitudinal water-proton MRI relaxivities of the gadolinium complexes at 7 T increased upon binding to HSA. On the basis of these results, the C-6 and C-7 compounds were identified as promising redox-sensitive MRI contrast agents.
Authors:
Bhumasamudram Jagadish; Gerald P Guntle; Dezheng Zhao; Vijay Gokhale; Tarik J Ozumerzifon; Ali M Ahad; Eugene A Mash; Natarajan Raghunand
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-11-28
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  55     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-13     Completed Date:  2013-02-26     Revised Date:  2013-12-18    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10378-86     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aza Compounds / chemistry,  pharmacology*
Contrast Media / chemistry,  pharmacology*
Heterocyclic Compounds, 1-Ring / chemistry,  pharmacology*
Magnetic Resonance Spectroscopy
Oxidation-Reduction
Spectrometry, Mass, Electrospray Ionization
Structure-Activity Relationship
Sulfhydryl Compounds / chemistry*
Grant Support
ID/Acronym/Agency:
P01 CA017094/CA/NCI NIH HHS; P01-CA017094/CA/NCI NIH HHS; P30-CA023074/CA/NCI NIH HHS; R01 CA118359/CA/NCI NIH HHS; R01-CA118359/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid; 0/Aza Compounds; 0/Contrast Media; 0/Heterocyclic Compounds, 1-Ring; 0/Sulfhydryl Compounds
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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