Method for improving blood anticoagulant activity of heparin

Abstract

A method for improving the blood anticoagulant activity of heparin takes conventional heparin as a substrate, takes PAPS (3'-phosphoadenosine-5'-phosphosulfate) as a sulfuric group donor, and uses a heparin biosynthetic enzyme 3-O-sulfotransferase (3-OST) for modifying the heparin to obtain heparin with high blood anticoagulant activity; The PAPS of the sulfuric group donor is generated by microbial fermentation, or extremely cheap PNPS (potassium p-nitrophenol sulfonate) is used as a sulfuric group donor for enzyme modification reaction. Through selective modification of the heparin, 3-site sulfated modification is increased, the number of blood anticoagulant active centers is increased, and thus the blood anticoagulant activity is greatly improved.

Description

Technical field [0001] The invention relates to a method for improving the anticoagulant activity of heparin, and belongs to the field of biochemical technology. Background technique [0002] As a widely used anticoagulant drug in clinical practice, heparin has been around 100 years since its discovery. However, the structure of heparin and its function in organisms are still not fully understood. Heparin and the related glycosaminoglycan heparan sulfate is a linear polysaccharide composed of uronic acid and amino sugar alternately connected by 1,4-glycosidic bonds. Uronic acid mainly contains β-D-glucuronic acid (GlcUA) and a small amount of α-L-iduronic acid (IdoUA). The amino sugar is composed of α-D-glucosamine (GlcN). There are also different substituent groups on the sugar chain. Uronic acid residues can be substituted by 2-O-sulfuric acid groups, while glucosamine residues can produce acetylamino, N-thio, 3-O-thio and / Or 6-O-thio group. It is the randomness and diver...

AI Technical Summary

Problems solved by technology

But the structure of heparin and its function in living organisms are still not fully understood