Linked Life Data

18804338

Source:http://linkedlifedata.com/resource/pubmed/id/18804338

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-10-20
pubmed:abstractText
Cationic Mn porphyrins are among the most potent SOD mimics and peroxynitrite scavengers. They have been widely and successfully used in different models of oxidative stress and are either progressing towards or are in phase I of clinical trials. The most frequently used compounds are Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+) or AEOL10113), its methyl analogue (MnTM-2-PyP(5+) or AEOL10112), and Mn(III) meso-tetrakis(4-benzoic acid)porphyrin (MnTBAP). A great discrepancy between the in vivo data obtained with Calbiochem preparations and those of authentic MnTE-2-PyP(5+) and MnTM-2-PyP(5+) samples were recently observed. Surprisingly, the commercial samples were invariably of poor identity and consisted of mixtures of nearly equal contributions of non-alkylated, mono-, di-, tri- and tetraalkylated porphyrins, lacking thus the major structural entity that determines their antioxidant potency, i.e., the four positively charged orthoN-alkylpyridyl groups that afford thermodynamic tuning of the active site and electrostatic guidance of anionic superoxide and peroxynitrite species toward the metal center. The MnTE-2-PyP(5+) and MnTM-2-PyP(5+) compounds were not even the major species in the commercial samples sold as "MnTE-2-PyP" and "MnTM-2-PyP", respectively. While we have already reported the insufficient impurity of the MnTBAP samples from Alexis and other suppliers, in one more recent lot the situation is dramatic, as 25% of the sample was not MnTBAP, but metal-free ligand, H(2)TBAP. The (unintentional) use of the Mn porphyrins of low quality compromises therapeutic and/or mechanistic conclusions. Simple techniques, which include thin-layer chromatography, electrospray-mass spectrometry, UV-vis spectroscopy, and electrochemistry described here could be used routinely to check the overall quality of Mn porphyrins in order to avoid misleading conclusions and waste of valuable resources (animals, compounds, time, manpower).
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0731-7085
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1046-9
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed-meshheading:18804338-Antioxidants, pubmed-meshheading:18804338-Binding Sites, pubmed-meshheading:18804338-Biomimetics, pubmed-meshheading:18804338-Chromatography, Thin Layer, pubmed-meshheading:18804338-Clinical Trials, Phase I as Topic, pubmed-meshheading:18804338-Electrochemistry, pubmed-meshheading:18804338-Free Radical Scavengers, pubmed-meshheading:18804338-Kinetics, pubmed-meshheading:18804338-Mass Spectrometry, pubmed-meshheading:18804338-Metalloporphyrins, pubmed-meshheading:18804338-Molecular Structure, pubmed-meshheading:18804338-Oxidation-Reduction, pubmed-meshheading:18804338-Peroxynitrous Acid, pubmed-meshheading:18804338-Physicochemical Phenomena, pubmed-meshheading:18804338-Spectrometry, Mass, Electrospray Ionization, pubmed-meshheading:18804338-Spectrophotometry, Ultraviolet, pubmed-meshheading:18804338-Static Electricity, pubmed-meshheading:18804338-Structure-Activity Relationship, pubmed-meshheading:18804338-Superoxide Dismutase
pubmed:year
2008
pubmed:articleTitle
Quality of potent Mn porphyrin-based SOD mimics and peroxynitrite scavengers for pre-clinical mechanistic/therapeutic purposes.
pubmed:affiliation
Department of Radiation Oncology, Duke University Medical School, Durham, NC 27710, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural