Saturated tetrasaccharide profile of enoxaparin. An additional piece to the heparin biosynthesis puzzle.
Carbohydr Polym
; 273: 118554, 2021 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-34560966
ABSTRACT
Enoxaparin, widely used antithrombotic drug, is a polydisperse glycosaminoglycan with highly microheterogeneous structure dictated by both parent heparin heterogeneity and depolymerization conditions. While the process-related modifications of internal and terminal sequences of enoxaparin have been extensively studied, very little is known about the authentic non-reducing ends (NRE). In the present study a multi-step isolation and thorough structural elucidation by NMR and LC/MS allowed to identify 16 saturated tetramers along with 23 unsaturated ones in the complex enoxaparin tetrasaccharide fraction. Altogether the elucidated structures represent a unique enoxaparin signature, whereas the composition of saturated tetramers provides a structural readout strictly related to the biosynthesis of parent heparin NRE. In particular, both glucuronic and iduronic acids were detected at the NRE of macromolecular heparin. The tetrasaccharides bearing glucosamine at the NRE are most likely associated with the heparanase hydrolytic action. High sulfation degree and 3-O-sulfation are characteristic for both types of NRE.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligossacarídeos
/
Heparina
/
Enoxaparina
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Carbohydr Polym
Ano de publicação:
2021
Tipo de documento:
Article