Inhibition of high-molecular-weight-(1-->3)-beta-D-glucan-dependent activation of a limulus coagulation factor G by laminaran oligosaccharides and curdlan degradation products.
Extensive surveys for the effects of various beta-D-glucans on the coagulation cascade in horseshoe crab amebocyte lysates showed that low-mol-wt-(1-->3)-beta-D-glucans and laminaran oligosaccharides inhibit the activation of a limulus coagulation factor G by high-mol-wt-(1-->3)-beta-D-glucans. The inhibitory properties are exclusively dependent upon their number-average mol wt (Mn) in a range of 342-58,100, which correspond to a degree of polymerization (dp) range of 2-359. The most effective is a laminaran dextrin of Mn 5800 (dp of 35-36), which causes 50% inhibition of factor G activation at a concentration of 3.16 ng/mL. The inhibition of the activation of factor G proportional to the concentration of the inhibitor, and the adsorption of factor G by inhibitory beta-D-glucan-conjugated cellulose suggested a high affinity of the inhibitory saccharides for the activator-recognition site of factor G. Branched (1-->6), (1-->3)-beta-D-glucans, laminarans, mixed linkage (1-->3), (1-->4)-beta-D-glucans, and partially substituted curdlan and laminaran were found to be inhibitory, possibly owing to clusters of consecutive (1-->3)-beta-D-glucopyranosyl residues as intrachain units. The inhibition appears to be related to the inability of the inhibitory (1-->3)-beta-D-glucans to form ordered conformations and to their tendency to take a random-coil structure in aqueous solution.
Tanaka
S
S
Tokyo Research Institute, Seikagaku Corporation, Japan.
Aketagawa
J
J
Takahashi
S
S
Shibata
Y
Y
Tsumuraya
Y
Y
Hashimoto
Y
Y
D000818:Animals; D000925:Anticoagulants; D001798:Blood Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005936:Glucans / Q000737:chemistry / Q000494:pharmacology*; D006737:Horseshoe Crabs; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D009844:Oligosaccharides / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology*; D011135:Polysaccharides, Bacterial / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D047071:beta-Glucans
D000925:Anticoagulants; D001798:Blood Proteins; D005936:Glucans; D008070:Lipopolysaccharides; D009844:Oligosaccharides; D011134:Polysaccharides; D011135:Polysaccharides, Bacterial; D047071:beta-Glucans; C013445:coagulogen; C038459:curdlan; C008247:laminaran