Sialic acids activity

Scheme 17.14 Synthesis of neo-sialocon- transfer to lactoside acceptor 36, respectively jugates by using a one-pot, two-step reaction [33, 34]. For reactions with sialic acid subcascade using CSS from Neisseria meningitidis strates carrying bulky N-acyl groups, the CSS and a2,6-SiaT from Photobacterium leiognathi variants engineered for that purpose were JT-SHIZ-145 for sialic acid activation and employed.

Factor V. High in sialic acid content. Factor V is a large asymmetric single-chain glycoprotein that becomes an active participant in the coagulation cascade when it is converted to its active form by a-thrombin. Approximately 25% of human Factor V is found in the whole blood associated with platelets. Factor V is an essential cofactor along with Factor Xa plus phosphohpid plus Ca " in the conversion of prothrombin to thrombin. 

The influenza virus inhibitors, zanamivir, and oseltamivir, act outside the cell after virus particles have been formed. The dtugs have been designed to fit into the active site of the viral envelope enzyme neuraminidase, which is required to cleave sialic acid off the surface of the producing cells. When its activity is blocked, new virus particles stay attached to the cell surface through binding of the virus protein hemagglutinin to sialic acid and are prevented from spreading to other cells. 

Kim CU, Lew W, Wilhams MA, Liu H, Zhang L, Swaminathan S, Bischofberger N, Chen MS, Mendel DB, Tai CY, Laver WG, Stevens RC (1997) Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity. J Am Chem Soc 119 681-690... 

As 2-amino-2-deoxy-D-mannose is tumorstatic and 2-acetamido-2-deoxy-D-mannose 6-phosphate is an obligatory intermediate in the biosynthetic pathway to sialic acid, displacement of the essential OH-6 with a fluorine atom should be interesting from the biological viewpoint. 2-Acetamido-1,3,4-tri-0-acetyl-2,6-dideoxy-6-fluoro-D-mannopyranose (see Table 111 in Section 11,3) and its O- and A,0-deacetyl derivatives were prepared the first compound showed weak anticancer activity. 

Incomplete (N-linked) glycosylation prompts decreased in vivo activity due to more rapid hepatic clearance of the EPO molecule. Enzymatic removal of terminal sialic acid sugar residues from oligosaccharides exposes otherwise hidden galactose residues. These residues are then free to bind specific hepatic lectins, which promote EPO removal from the plasma. The reported plasma tm value for native EPO is 4-6 h. The tm for desialated EPO is 2 min. Comparison of native human EPO with its recombinant form produced in CHO cells reveals very similar glycosylation patterns. 

Parallel synthesis of 62 different fucosylated tripeptides resulted in two ligands with submicromolar affinity for the P-selectin however, the desired activity for the E-selectin was not observed.98 For the E-selectin selectivity, it was necessary to incorporate a hydroxyl group that mimics the 4-hydroxyl of the central Gal in SLex in addition to a Fuc-residue and a carboxylate to obtain ligands with > 10-fold increased activity over that of the SLex tetrasaccharide.81 One of the best ligands was obtained from Thr(a-Fuc)-OEt, which was first /V-acylated with a hydroxyl amino acid and then elongated with a di-acid to furnish the acid mimic of the sialic acid carboxylate (Fig. 14.4). This approach was further developed as a solid-phase method where the molecule was linked to a solid support through the invariable fucosyl moiety.99... 

C5-derived peptide in serum. This molecule lacks anaphylatoxin activity (i.e. it cannot cause smooth muscle contraction), and its ability to cause che-motaxis in neutrophils is about 10-20 times lower than that of C5a. However, human serum also contains a heat-stable, anionic protein termed co-chemotaxin (relative molecular mass = 60 kDa), which acts in a concentration-dependent manner to permit C5a des Arg to act as a chemoattractant for neutrophils. Thus, C5a des Arg plus cochemotaxin working together probably account for most of the neutrophil chemoattractant activity in vivo following complement activation. The mechanism of action of cochemotaxin is unknown, but it may form a physical complex by attaching to a sialic acid residue on the oligosaccharide chain of C5a des Arg. Deglycosylation of C5a des Arg increases its chemoattractant activity more than 10-fold, and its dependency upon cochemotaxin is decreased. 

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