The long-range objective of the proposal is to develop plasma membrane modifiers and inhibitors affecting the viability and social behavior of the cancer cells and hopefully increasing their immunogenicity and permeability with respect to anti-cancer drugs. The following approaches will be attempted: (1) Analogs of certain amino sugars (D-glucosamine, D-galactosamine, D-mannosamine, and sialic acid) and of L-fucose and 6-deoxy-D-mannose) will be synthesized and tested in various systems, among which those designed to determine changes in cell membrane function are given prominence. (2) Potential inhibitors of cell surface glycosyltransferases, viz. some nucleotide sugar analogs, will be prepared. The effect of certain hydrophobic compounds on the cell membrane will also be evaluated. Biological and biochemical testing of the compounds will be carried out in hexokinase and on P288 murine leukemia cells both in vitro and in vivo. In vitro tests are designed to evaluate the effect of the compounds on cell growth and on the synthesis of glycoprotein and protein membrane components. In vivo tests are primarily designed to detect changes in membrane function or antigenicity. BIBLIOGRAPHIC REFERENCES: Korytnyk, W. and Potti, P.G.G. Antagonists of Vitamin B6. Simultaneous and Stepwise Modification of the 2 and 4 Positions, J. Med. Chem. 20, 1(1977). Hanchak, M. and Korytnyk, W., Studies of the epimerization of 2-Acetamido-2-deoxy-D-glucopyranose: Selective deuteration of C-2 in Acetamido-2-deoxyladoses. Carbohydrate Research, In Press, 1977.
NIH ExPorter
NIH ExPorter