Structural requirements for active intestinal transport. Spatial and bonding requirements at C-3 of the sugar.
Analogues of d-glucose modified at C-3, and in some cases at a second position, were prepared and tested for active accumulation by everted segments of hamster intestine. Their relative affinity for the sugar carrier was measured by tissue/medium ratio, Michaelis-Menten kinetics and competitive inhibition of d-galactose or methyl alpha-d-glucoside transport. d-Glucose and its 3-deoxy-3-fluoro, 3-chloro-3-deoxy and to a smaller extent its 3-bromo-3-deoxy derivatives, bound and were transported more strongly than 3-deoxy-d-glucose and other sugars not containing an electronegative atom in the gluco configuration at C-3. 3-Deoxy-d-galactose, 3,6-dideoxy-d-glucose and d-gulose, which have two alterations from the d-glucose structure, were not, or only very weakly, transported. The results are interpreted as indicating the presence of a hydrogen bond from the carrier to the hydroxyl group at C-3 of d-glucose. Spatial requirements are also discussed. New syntheses are reported for 3-chloro-3-deoxy- and 3-bromo-3-deoxy-d-glucose and 3,6-dideoxy-d-glucose.
D000818:Animals; D001693:Biological Transport, Active; D001965:Bromides; D002712:Chlorides; D006224:Cricetinae; D005459:Fluorides; D005690:Galactose / Q000378:metabolism; D005947:Glucose / Q000138:chemical synthesis / Q000378:metabolism*; D006027:Glycosides / Q000378:metabolism; D006601:Hexoses / Q000378:metabolism; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism; D007700:Kinetics
D001965:Bromides; D002712:Chlorides; D006027:Glycosides; D006601:Hexoses; D005947:Glucose; D005459:Fluorides; D005690:Galactose
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