We will continue studies on the attachment of carbohydrates to enzymes and nonenzymic proteins to give soluble carbohydrate-protein conjugates. We will compare, in vitro, properties of native and conjugated enzymes, in particular the effect of different carbohydrates and different coupling procedures on the stability properties and other characteristics of the conjugates. The bahavior of conjugated proteins and enzymes in experimental animals will be investigated, with particular regard to defining the characteristics of the conjugates that determine their behavior in vivo, and we will evaluate their possible applications as therapeutic agents, for example in the treatment of inborn errors of metabolism and other metabolic disorders. Thus we will investigate in detail the effect of different carbohydrates on the immunological properties and circulatory lifetimes of conjugated proteins, and study the "homing" of conjugates to different organs and tissues. Experimental enzyme therapy will be conducted with conjugated enzymes, using experimental animals and cultured cells. We will prepare carbohydrate derivatives of L-asparaginase and test their effectiveness as anti-tumor agents in animals bearing implanted lymphosarcomas; it is hoped that the usefulness of this enzyme as an anti-tumor agent can be improved by coupling with carbohydrate, by virtue of extension of the circularity lifetime of the enzyme and elimination of the allergic reactions associated with its use. The properties of cyclodextrin-albumin as a drug carrier will be evaluated. Attempts will be made to develop blood substitutes by conjugation of hemoglobin with polysaccharides such as hydroxyethyl starch and dextran.
NIH ExPorter
NIH ExPorter