Preparation of gellan sulfate as an artificial ligand for removal of extra domain A containing fibronectin.
The extra domain A containing fibronectin (EDA(+)FN) concentration in plasma of rheumatoid arthritis (RA) is abnormally higher than the normal level. We synthesized various gellan-sulfate (GS) candidates as artificial ligands for removing EDA(+)FN from plasma. The interaction between these artificial ligands and EDA(+)FN was evaluated using affinity constants (KA), which were determined by surface plasmon resonance measurement. The KA (3.6 x 10(8) per M) of GS-25 [degree of substitution for sulfonation (DS) = 25%] with EDA(+)FN was higher than those of other molecules: GS-16 (DS=16%) at 8.3 x 10(7) per M, and GS-35 (DS = 35%) at 1.7 x 10(8) per M. Furthermore, GSs displayed selectivity of EDA(+)FN for binding with plasma FN (KAEDA(+)FN)/KA(plasma FN)>2). The removal ratio in plasma was measured by using GS-immobilized gel. Removals of 66, 11, 7.7, 6.2, 6.9, and 12% for EDA(+)FN, plasma FN, fibrinogen, albumin, immunoglobulin G (IgG) and antithrombin III from the patient-model plasma were, respectively, achieved with GS-25-immobilized gel. These results suggest that GS may be used as a selective artificial ligand for EDA(+)FN removal from plasma in RA treatment.
Miyamoto
K
K
Department of Chemistry for Materials, Faculty of Engineering, Mie University, 1515 Kamihama-chou, Tsu, 514-5807, Mie, Japan. miyamoto@chem.mie-u.ac.jp
Asakawa
Y
Y
Arai
Y
Y
Shimizu
T
T
Tokita
M
M
Komai
T
T
D000327:Adsorption; D001798:Blood Proteins / Q000737:chemistry*; D005353:Fibronectins / Q000097:blood* / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D020349:Surface Plasmon Resonance
D001798:Blood Proteins; D005353:Fibronectins; D008024:Ligands; D011135:Polysaccharides, Bacterial; C048288:gellan gum