Synthesis and characterization of a novel paramagnetic macromolecular complex [Gd(TTDASQ-protamine)].
Adenocarcinomas in rats and humans frequently contain perivascular, degranulating mast cells that release heparin. Protamine is a low-molecular weight, cationic polypeptide that binds to heparin and neutralizes its anticoagulant properties. A novel magnetic resonance imaging (MRI) contrast agent containing protamine was synthesized. TTDASQ, the derivative of TTDA (3,6,10-tri(carboxymethyl)-3,6,10-triazadodecanedioic acid), was also synthesized and the kinetic stability of [Gd(TTDASQ)]- chelate containing phosphate buffer and ZnCl2 to measure the relaxation rate (R1) at 20 MHz was studied by transmetallation with Zn(II). The water-exchange rate (k(ex)298) of [Gd(TTDASQ)]- is 6.4 x 10(6) s(-1) at 25.0 +/- 0.1 degrees C which was obtained from the reduced 17O relaxation rates (1/T(1r) and 1/T(2r)) and chemical shift (omega(r)) of H(2)17O, and it is compared with that previously reported for the other gadolinium(III) complex, [Gd(DO3ASQ)]. The binding affinity assay showed that the (TTDASQ)3-pro19 has higher activity toward heparin. On the other hand, the effect of heparin on the relaxivity of the [Gd(TTDASQ)3-pro19] conjugate shows the binding strength (K(A)) is 7669 dm3 mol(-1) at pH 7.4 and the relaxivity (r(b)1) of the [Gd(TTDASQ)3-pro19]-heparin adduct is 30.9 dm3 mmol(-1) s(-1).
Cheng
Tsan-Hwang
TH
Department of Biological Science and Technology, Chung Hwa College of Medical Technology, 89, Wunhua 1st Street, Rende Township, Tainan County, 717, Taiwan, ROC.
Lee
Wei-Tsung
WT
Jeng
Jie-Shiunh
JS
Wu
Ching-Ming
CM
Liu
Gin-Chung
GC
Chiang
Michael Yen Nan
MY
Wang
Yun-Ming
YM
D003503:Cyclobutanes / Q000138:chemical synthesis / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D046911:Macromolecular Substances / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008280:Magnetics; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D011479:Protamines / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013696:Temperature
C516311:6-(2-hydroxy-3,4-dioxo-1-cyclobutenyl)-3,6,10-triazadodecane-3,10-tetraacetic acid; D003503:Cyclobutanes; D008024:Ligands; D046911:Macromolecular Substances; D009942:Organometallic Compounds; D011479:Protamines; D005682:Gadolinium; D005998:Glycine