Synthesis of a Systematic 64-Membered Heparan Sulfate Tetrasaccharide Library.
Angew Chem Int Ed Engl
; 62(1): e202211985, 2023 01 02.
Article
em En
| MEDLINE
| ID: mdl-36173931
ABSTRACT
Heparan sulfate (HS) has multifaceted biological activities. To date, no libraries of HS oligosaccharides bearing systematically varied sulfation structures are available owing to the challenges in synthesizing a large number of HS oligosaccharides. To overcome the obstacles and expedite the synthesis, a divergent approach was designed, where 64 HS tetrasaccharides covering all possible structures of 2-O-, 6-O- and N-sulfation with the glucosamine-glucuronic acid-glucosamine-iduronic acid backbone were successfully produced from a single strategically protected tetrasaccharide intermediate. This extensive library helped identify the structural requirements for HS sequences to have strong fibroblast growth factor-2 binding but a weak affinity for platelet factor-4. Such a strategy to separate out these two interactions could lead to new HS-based potential therapeutics without the dangerous adverse effect of heparin-induced thrombocytopenia.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligossacarídeos
/
Heparitina Sulfato
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos