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Abstract

Colominic acid is an alpha2,8-linked sialic acid polymer produced by Escherichia coli. We found that synthetic sulfated-colominic acids (SC) remarkably inhibited the cytotoxicity of bee and snake venom toward mouse fibroblast cells, but colominic acids showed no inhibition themselves, indicating the important role of sulfate groups in the inhibitory activity of SC. Other sulfated carbohydrates such as chondroitin sulfates, heparin and heparan sulfate showed no inhibition. SC also exhibited potent inhibition of melittin, a highly basic peptide, which is a major cytotoxic component of bee venom. SC did not inhibit phospholipase A2 activity in bee venom. This suggests that the inhibition of bee and snake venom by SC is due to inhibition of melittin and cardiotoxin, which is a cytolytic peptide in snake venom, respectively. SC with a higher sulfur content and a larger molecular mass showed more potent activity. The interaction between SC and melittin basically seems an ionic one, however, the conformation of SC is also likely important. For the binding of SC to melittin leading loss of its cytotoxic activity, the sulfate groups of SC must be properly arranged to interact with lysine and arginine residues of melittin molecules, which play an important role in the cytolytic activity. A higher molecular mass of SC substituted with more sulfate groups is required for more obvious inhibition of the cytotoxic activity.

Deciphering Isomers with a Multiple Reaction Monitoring Method for the Complete Detectable O-Glycan Repertoire of the Candidate Therapeutic, Lubricin

“…Little is known about the biological significance of the sulfated Neu5Ac, primarily due to the difficultly in analyzing this unstable structure. It has been detected in a limited range of biological samples, including sea urchin sperm and eggs. , Sulfated sialic acids have also been shown to have potentially critical pathogen and binding blocking roles, including in blocking HIV infection, blocking of L- and P-selectin dependent cobra venom factor binding, as well as inhibiting the cytotoxic effects of other snake venoms and bees and inhibition of in vitro fertilization of mice, although all of these studies have centered on low molecular mass sulfated Neu5Ac (2,8-linked Neu5Ac) polymers. The importance of the sulfated sialylated structures observed here on lubricin, a critical lubricating molecule of the human joint, is currently unknown and is of particular interest, given that the boundary lubrication imparted by lubricin provides both a low binding and low friction surface to the joint. − It is essential to have subtle and sensitive methods, such as the method demonstrated here, to be able to continue such detailed O -glycan analyses to allow the comprehensive understanding of these poorly understood glycans.…”

Inhibition of Cultured Bovine Aortic Smooth Muscle Cell Proliferation by Colominic Acid

“…It has been shown that several biological activities of SCA also require the sulfate group. 2,[6][7][8] Thus, the sulfation appears to be in general essential for exhibition or intensification of the biological activities of polysaccharides. In contrast, the present data showed that the inhibitory effect of CA on vascular smooth muscle cell proliferation is unaffected by the sulfation, suggesting that the polysaccharide chain structure of CA interacts for itself with the cells and the sulfate group does not influence the interaction.…”

“…2) have several biological activities including antiviral activities, [3][4][5] inhibition of the cytotoxic action of bee and snake venom, 6) inhibition of P-selectin-dependent macrophage infiltration in the glomeruli in experimental rat crescentic glomerulonephritis 7) and inhibition of fertilization of mouse gametes. …”

“…Sulfated CA (SCA), prepared by the chemical sulfation of CA, 2) have several biological activities including antiviral activities, [3][4][5] inhibition of the cytotoxic action of bee and snake venom, 6) inhibition of P-selectin-dependent macrophage infiltration in the glomeruli in experimental rat crescentic glomerulonephritis 7) and inhibition of fertilization of mouse gametes. 8) Atherosclerosis is the principal vascular lesion in the pathogenesis of myocardial and cerebral infarction, which is initiated by vascular endothelial cell damage followed by an intimal hyperplasia of vascular smooth muscle cells.…”