Glycoproteins from tumor cells

Examples of the use of analytical-scale column systems for the small-scale (i.e., 1 fig to 1 mg) preparative separation of peptides include the extraordinarily potent opoid peptide, dynorphin (I4S) insulin A-, B-, and C-chain peptides (24, 72) j8-chain peptides of the pituitary glycoprotein hormones (8) endorphins (28,60, 126, 137), adrenocorticotropic peptides in plasma, pituitary, and other endocrine glands or secreted from tumor cells iVt vitro (84, I2S, 127, 138, 142. I Si) hypothalamic releasing factors... 

Multidrug resistance is observed in tumor cell populations exposed to anthracyclines. Attempts to reverse or prevent the emergence of resistance through the simultaneous use of inhibitors of P-glycoprotein, such as Ca channel blockers, steroidal compounds, and others, have yielded inconclusive results, primarily because of the effects of these inhibitors on anthracycline pharmacokinetics and metabolism. Anthracyclines also are exported from tumor cells by members of the MRP transporter family and by the breast cancer resistance protein. Other biochemical changes in resistant cells include increased glutathione peroxidase activity, decreased activity or mutation of topoisomerase II, and enhanced ability to repair DNA strand breaks. 

N-Acetvlneuraminic Acid Aldolase. A new procedure has also been developed for the synthesis of 9-0-acetyl-N-acetylneuraminic acid using the aldolase catalyzed reaction methodology. This compound is an unusual sialic acid found in a number of tumor cells and influenza virus C glycoproteins (4 ). The aldol acceptor, 6-0-acetyl-D-mannosamine was prepared in 70% isolated yield from isopropenyl acetate and N-acetyl-D-mannosamine catalyzed by protease N from Bacillus subtilis (from Amano). The 6-0-acetyl hexose was previously prepared by a complicated chemical procedure (42.) The target molecule was obtained in 90% yield via the condensation of the 6-0-acetyl sugar and pyruvate catalyzed by NANA aldolase (Figure 6). With similar procedures applied to KDO, 2-deoxy-NANA and 2-deoxy-2-fluoro-NANA were prepared from NANA. 

Smyth MJ, Drasovskis E, Sutton VR, Johnstone RW (1998) The drug efflux protein, P-glycoprotein, additionally protects drug-resistant tumor cells from multiple forms of caspase-dependent apoptosis. Proc Natl Acad Sd USA 95 7024-7029... 

Meschini, S., Marra, M., Condello, M., Calcabrini, A., Federici, E., Dupuis, M. L., Cianfriglia, M. and Arancia, G. 2005. Voacamine, an alkaloid extracted from Peschiera fuchsiaefolia, inhibits P-glycoprotein action in multidrug-resistant tumor cells. International Journal of Oncology, 27(6) 1597-1603. 

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