Glycoproteins therapeutic

Carbohydrates play a major role in protein bioactivity, bioavailability, and antigenicity therefore, the understanding of the glycosylation of protein molecules is very important in the development of effective glycoprotein therapeutics.172 In recent years, there has been considerable activity in the development of simple, rapid, and reliable separation methods for the analysis of... 

Raju TS, Briggs JB, Borge SM, Jones AJ (2000), Species-specific variation in glycosylation of IgG evidence for the species-specific sialylation and branch-specific galactosylation and importance for engineering recombinant glycoprotein therapeutics, Glycobiology 10 477-486. 

EoUowing po administration moricizine is completely absorbed from the GI tract. The dmg undergoes considerable first-pass hepatic metabolism so that only 30—40% of the dose is bioavailable. Moricizine is extensively (95%) bound to plasma protein, mainly albumin and a -acid glycoprotein. The time to peak plasma concentrations is 0.42—3.90 h. Therapeutic concentrations are 0.06—3.00 ]l/niL. Using radiolabeled moricizine, more than 30 metabolites have been noted but only 12 have been identified. Eight appear in urine. The sulfoxide metabolite is equipotent to the parent compound as an antiarrhythmic. Elimination half-life is 2—6 h for the unchanged dmg and known metabolites, and 84 h for total radioactivity of the labeled dmg (1,2). 

Not all transporters, however, show the same preferential directions. Lee and coworkers also have discovered a pump glycoprotein in the conjunctiva with preferential flux directed toward the mucosal side of the tissue. This transporter has been shown to restrict conjunctival absorption of therapeutic agents such as cyclosporin A, verapamil, and dexamethasone. In some circumstances, transient inhibition of such xe-nobiotic transporters might be an effective means of increasing the efficacy of particular classes of therapeutic agents. 

In the tight of the results presented above, we conclude that alfalfa offers a suitable system for the high-yield production of correctly assembled complex proteins, including multimeric glycoproteins. The post-translational capacities of alfalfa indicate that this system is one of the best-suited for the production of molecules for therapeutic and diagnostic applications. 

Most therapeutic proteins are glycoproteins, and in this chapter we discuss the advantages and limitations of glycosylation when mammalian proteins and particularly antibodies are produced in plant expression systems. 

---