Xylopyranoside-based agonists of D-myo-inositol 1,4,5-trisphosphate receptors: synthesis and effect of stereochemistry on biological activity.
Carbohydr Res
; 332(1): 53-66, 2001 May 08.
Article
em En
| MEDLINE
| ID: mdl-11403088
ABSTRACT
The synthesis of a series of tetrahydrofuranyl alpha- and beta-xylopyranoside trisphosphates, designed by excision of three motifs of adenophostin A is reported. The synthetic route features improved preparations of allyl alpha-D-xylopyranoside and its 2-O-benzyl ether, and gives access to four diastereoisomeric trisphosphates, which show a range of abilities to mobilise Ca2+ from the intracellular stores of hepatocytes. A comparison of the potencies of the four trisphosphates provides useful information relating to the effects of stereochemical variation on the recognition of carbohydrate-based trisphosphates by D-myo-inositol 1,4,5-trisphosphate receptors. 1-O-[(3'S,4'R)-3-hydroxytetrahydrofuran-4-yl] alpha-D-xylopyranoside 3,4,3'-trisphosphate (8) is the most active member of the series with a potency close to Ins(1,4,5)P3; a beta-linked analogue, 1-O-[(3'R,4'S)-3-hydroxytetrahydrofuran-4-yl] beta-D-xylopyranoside 3,4,3'-trisphosphate, is ca. 20-fold weaker than Ins(1,4,5)P3, and the other compounds are much less active. While no compound attained a potency close to that of adenophostin A, we believe that 8 represents the minimal structure for potent Ca2+-releasing activity in this type of carbohydrate-based analogue.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Xilose
/
Receptores Citoplasmáticos e Nucleares
Limite:
Animals
Idioma:
En
Revista:
Carbohydr Res
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Reino Unido