Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.

Galina Linden

Abraham J Domb

Shimon Benita

Itzhack Polacheck

A method for producing a water-soluble polysaccharide conjugate of an oxidation-sensitive substance is described. The method comprises the following steps: (a) activating the polysaccharide to a dialdehyde by periodate oxidation; (b) purifying the dialdehyde from interfering anions and by-products; and (c) coupling the substance to the purified dialdehyde by Schiff base formation to form the conjugate. Optionally, the conjugate of step (c) is reduced to an amine conjugate by a reducing substance. The product conjugate may then be further purified from various reaction byproducts. The disclosed method results in the substance substantially retaining its biological activity. Also described are imine and amine polysaccaride conjugates of various drugs and polypeptides.

Conjugates of biologically active substances

A method for producing a substantially stable water-soluble polysaccharide conjugate of a polyene antibiotic is described. The method comprises the following steps: (a) activating the polysaccharide to a dialdehyde by periodate oxidation; (b) purifying the dialdehyde from interfering anions and by-products; (c) coupling the polyene to the purified dialdehyde by Schiff base formation to form the conjugate; and (d) purifying the conjugate. In a preferred embodiment, the conjugate of step (c) is reduced to an amine conjugate by a reducing agent prior to purification. Also described are imine and amine polysaccaride conjugates of the polyene Nystatin.

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Bat Yam, Israel

Galina Linden