Glycosylation process

TABLE 9-1 Compartmentalization of glycosylation processing steps in the secretory pathway... 

Therefore, to obtain complete stereoselectivity, the entire glycosylation process has to be performed in a highly controlled manner. In this particular case, the control is achieved by the use of extremely mild catalyst (I NBr), although very reactive substrates and prolonged reaction at times are required. 

The glycosylation process by using the trisaccharide fluoride is repeated twice to give trimeric Lex61 after deprotections. 

The sulfoxide method was employed in the direct synthesis of a P-l,2-man-nooctaose (Scheme 4.60) [362-364]. The synthesis of a p-mannosyl phosphoiso-prenoid illustrates the possibility of employing even such weak nucleophiles as phosphates (Scheme 4.61) [365]. Both syntheses rely on the presence of 4,6-0-benzylidene acetal, and its effect on the covalent triflate-contact ion-pair equilibrium [366,367], to influence the stereochemistry of the glycosylation process [295,323],... 

The concentration of dolichyl phosphate in eukaryotic tissues is very low and is probably rate-limiting for the glycosylation processes. Variation of the concentration in the endoplasmic-reticulum membranes is a possible way of controlling the rate of glycosylation. It is important to point out that the early steps in the dolichol biosynthesis are common to such other prenyl derivatives in plants as steroids, essential oils, hormones, phytol, and carotenes (see Scheme 1), and parameters affecting those reactions that may control the dolichol to dolichyl phosphate step could be another mechanism for regulation of the level of dolichyl phosphate. 

Bellenamine, (R)-3,6-diamino-V-(aminomethyl)hexanamide is a (very) small-molecular-weight (MW 174) antibiotic produced by Streptomyces nashvillensis. It has only weak antibacterial activity but inhibits HIV-1 infection at an IC50 of 0.62 pg/ml (3.6 iM). With a CC50 of > 2 mg/ml (11.5 mM), the selectivity index of bellenamine can be estimated at well above 2000. Similarl to the well-established glycosylation inhibitors castanospermine and 1-deoxynojirimycin, bellenamine inhibits the secondary spread of HIV, although, unlike the glycosylation inhibitors, bellenamine had no apparent inhibitory effect on the glycosylation process. Therefore, its antiviral mechanism remains to be elucidated. 

FIGURE 3.10 Mitsunobu glycosylation process R side-chain amino acids P protective group or resin linker. 

R., Acharya, K. R., Sturrock, E. D., De-glycosylation, processing, and crystallization of human testis angiotensin-converting enzyme. Bioohem. J. 2003, 373, 437-442... 

A second posttranslation modification that occurs in the maturation of collagen is the oxygenation of lysine residues to form 5-e/yfAro-hydroxylysine, which serves as an anchor for attachment of carbohydrates in a glycosylation process (equation 2). 

---