Overview of the current procedures in synthesis of heparin saccharides.
Carbohydr Polym
; 339: 122220, 2024 Sep 01.
Article
in En
| MEDLINE
| ID: mdl-38823902
ABSTRACT
Natural heparin, a glycosaminoglycan consisting of repeating hexuronic acid and glucosamine linked by 1 â 4 glycosidic bonds, is the most widely used anticoagulant. To subvert the dependence on animal sourced heparin, alternative methods to produce heparin saccharides, i.e., either heterogenous sugar chains similar to natural heparin, or structurally defined oligosaccharides, are becoming hot subjects. Although the success by chemical synthesis of the pentasaccharide, fondaparinux, encourages to proceed through a chemical approach generating homogenous product, synthesizing larger oligos is still cumbersome and beyond reach so far. Alternatively, the chemoenzymatic pathway exhibited exquisite stereoselectivity of glycosylation and regioselectivity of modification, with the advantage to skip the tedious protection steps unavoidable in chemical synthesis. However, to a scale of drug production needed today is still not in sight. In comparison, a procedure of de novo biosynthesis in an organism could be an ultimate goal. The main purpose of this review is to summarize the current available/developing strategies and techniques, which is expected to provide a comprehensive picture for production of heparin saccharides to replenish or eventually to replace the animal derived products. In chemical and chemoenzymatic approaches, the methodologies are discussed according to the synthesis procedures building block preparation, chain elongation, and backbone modification.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Heparin
/
Anticoagulants
Limits:
Animals
Language:
En
Journal:
Carbohydr Polym
Year:
2024
Document type:
Article
Affiliation country: