IgGl molecule

Figure 31-6 Three-dimensional ribbon representation of the structure of a complex of a soluble Fc fragment of a human IgGl molecule. Pro 329 of the IgG and Trp 87 and Trp 110 of the Fc-receptor fragment form a "proline sandwich/ which is shown in ball-and-stick form. The oligosaccharide attached to the Fc fragment of the antibody and the disulfide bridge between the two Cys 229 residues (at the N termini of the C2 domains of the heavy y chains) are also shown. The small spheres on the Fc receptor fragment are potential sites for N-glycosylation. From Sondermann et al.107 Courtesy of Uwe Jacob.

IgGl molecule. Consequently, an artificial antibody is constituted with two Fab sites, which are soluble human 75-kDa TNF-a receptors. It competitively inhibits the binding of TNF molecules to the TNF receptor sites. The binding of etaner-cept to TNF renders the bound TNF biologically inactive, resulting in the reduction of the inflammatory activity. The most frequent adverse side effects are injection site reactions, infections and headache and malignancies are rare. Etanercept is not recommended for patients with serious infections or sepsis and does not appear to result in the reactivation of tuberculosis. 

Compared to small-molecule dmgs, therapeutic mAbs display different pharmacokinetic characteristics, including nonlinear pharmacokinetic behavior. As the majority of therapeutic mAbs present IgG (or more specially IgGl) molecules, the emphasis will be placed on this isotype, although the characteristics of newer types of molecule such as antibody fragments will also be included. 

Micouin A, Rouillard D, Bauvois B. Induction of macrophagic differentiation and cytokine secretion by IgGl molecules in human normal monocytes and myelogenous leukemia cells. Leukemia 1997 ll(4) 552-60. 

Etanercept inhibits the activity of the cytokine, TNF (see p. 280). It is a dimeric fusion protein of two TNF receptors (called p75) joined to the Fc domain (constant region) of a human IgGl molecule. One... 

In the present case, all IgGl molecules contain a conserved N-glycosylation site at asparagine 297 in the constant region of the molecule. In human serum, the major... 

Fig. 3.23 Structures of the three most common glycans found in human IgGl molecules, GO, Gl, and G2.

In the heavy-chain hinge fragment 225-232 the intervening sequence between the two cysteine residues is Pro-Pro and the native structure of this portion of the IgGl molecule consists of a parallel dimer. By estimating for the Cys-Pro-Pro-Cys portion the propensity for chain reversal, l.e. for p-tum formation, according to... 

A single H chain may possess more than one Gm determinant for example, IgGl molecules of Caucasians frequently have three Gm markers Gm(l) and Gm(2) on fragment Fc and Gm(17) on fragment Fd (Table 9.5). 

The glycans on a recombinant IgG antibody, eg. plantibody , produced in transgenic tobacco plants have recently been compared with the carbohydrates on the complementary IgGl molecule, (Guy slS antibody) produced in a murine monoclonal cell line (Figure 8) [72] Four major biantennary glycan structures were... 

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