Analogs of Eu3+ DOTAM-Gly-Phe-OH and Tm3+ DOTAM-Gly-Lys-OH: synthesis and magnetic properties of potential PARACEST MRI contrast agents.
Chelated lanthanide ions, especially gadolinium, have found wide use as contrast agents in magnetic resonance imaging. A new paradigm for generating contrast, termed PARACEST, was recently described that requires the slow exchange of water or other exchangeable protons present in the ligand framework. In previous work, we have described a synthetic method for the preparation of dipeptide conjugates of DOTAM for use as PARACEST agents. Two compounds possessed interesting magnetic properties: the Eu(3+) complex of DOTAM-Gly-Phe-OH and the Tm(3+) complex of DOTAM-Gly-Lys-OH. To understand the relationship between the structure of these complexes and their magnetic properties, we have expanded our synthetic methodology and prepared several new complexes. Ligands have been prepared in which the terminal phenylalanine moieties have been replaced with tryptophan or tyrosine, the distance to the amino acid residue possessing an alpha-substituent has been changed, or phenylalanine and lysine have been combined in the peptide sequence. The preparation of lanthanide(III) complexes of these ligands has been achieved and their PARACEST properties have been determined.
Suchý
Mojmír
M
Department of Chemistry, The University of Western Ontario, Chemistry Building, Room 209, London, Ont., Canada N6A 5B7.
Li
Alex X
AX
Bartha
Robert
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Hudson
Robert H E
RH
D000081:Acetamides / Q000138:chemical synthesis*; D003287:Contrast Media / Q000138:chemical synthesis*; D000080027:Cyclams; D004151:Dipeptides / Q000138:chemical synthesis*; D005063:Europium; D005998:Glycine / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis*; D008024:Ligands; D008239:Lysine / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D010649:Phenylalanine / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013932:Thulium
C522450:1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane; D000081:Acetamides; D003287:Contrast Media; D000080027:Cyclams; D004151:Dipeptides; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D008024:Ligands; D005063:Europium; D010649:Phenylalanine; D013932:Thulium; C038072:cyclen; D008239:Lysine; D005998:Glycine