Design, synthesis, and evaluation of 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid derived, redox-sensitive contrast agents for magnetic resonance imaging.
The design and synthesis of three 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) derivatives bearing linkers with terminal thiol groups and a preliminary evaluation of their potential for use in assembling redox-sensitive magnetic resonance imaging contrast agents are reported. The linkers were selected on the basis of computational docking with a crystal structure of human serum albumin (HSA). Gd(III)-DO3A and Eu(III)-DO3A complexes were synthesized, and the structure of one complex was established by X-ray crystallographic analysis. The binding to HSA of a Gd(III)-DO3A complex bearing a thiol-terminated 3,6-dioxanonyl chain was competitively inhibited by homocysteine and by the corresponding Eu chelate. Binding to HSA was abolished when the terminal thiol group of this complex was absent. The longitudinal water-proton relaxivities (r(1)) of the three Gd(III)-DO3A complexes and of two Gd(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complexes were measured in saline at 7 T. The DO3A complexes exhibited smaller r(1) values, in both bound and free states, than the DOTA complexes.
Raghunand
Natarajan
N
Department of Radiology, University of Arizona, Tucson, Arizona 85724-5024, USA.
Guntle
Gerald P
GP
Gokhale
Vijay
V
Nichol
Gary S
GS
Mash
Eugene A
EA
Jagadish
Bhumasamudram
B
D001667:Binding, Competitive; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D005063:Europium; D005682:Gadolinium; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry; D013329:Structure-Activity Relationship
C520644:1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid; D003287:Contrast Media; D056831:Coordination Complexes; D006573:Heterocyclic Compounds, 1-Ring; D012709:Serum Albumin; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D005063:Europium; D005682:Gadolinium