Trehalose covalently conjugated to bovine serum albumin

Synthesis and immunomodulating tumor control properties of albumin covalently connected to trehalose

“…The sequence of reactions leading to 10 resembled that used for the bis-amino intermediate 5, HOCHz 1 o, J2 (11) except that the starting point was trehalose derivative 7, having only one open hydroxyl group [7]. Thus, after monoacylation of 7 with p-nitrophenylacetyl benzenesulfonate, hydrogenation of the resulting ester 8 gave monoamine 9.…”

“…Since, in the first instance, the point of connection between the sugar moiety and the protein was to involve only the trehalose primary hydroxyl groups (i.e., positions 6 and 6'), we started with a trehalose derivative 2 in which all the hydroxyl groups were masked with trimethylsilyl except the primary ones [7]. Acylation with the mixed anhydride, p-nitrophenylacetyl benzenesulfonate, attached the group serving to link the sugar to the protein where it was wanted, i.e., at the trehalose 6,6' positions (cf.…”

“…Since the earlier samples of bovine serum albumin covalently conjugated with 6,6-bis-(p-aminobenzoyl)-trehalose [7] were exhausted, it was necessary to repeat the preparation. The new material 12a incorporated 8.6 molecules of prosthetic group per molecule of bovine serum albumin.…”

“…The earlier persilylation procedure [7] was significantly improved in that it was found unnecessary to dehydrate trehalose before silylating, or to distill the product. The reactants taken were 6.8 g (19 retool) D(+)-trehalose dihydrate, 35 ml (250 retool) trimethylsilyl chloride, and 125 mt pyridine.…”

“…This was prepared essentially as described before [7]. In the last desilylation step, however, crystallization from 1 : 1 methanol-chloroform gave the product (86%) in the form of shiny plates; mp 116 °-119 °.…”