Sadana and Vo-Dinh (1997) have developed a model for multivalency antibodies for large antigen systems. These authors presented a theoretical analysis of the influence of multivalency of antigen on external mass transfer-limited binding kinetics to divalent antibodies for biosensor applications to polycyclic-aromatic systems. The design of antibody-targeted agents for a large class of chemical species such as polycyclic-aromatic compounds (PACs) could be an important development for biosensors. Such biosensors could be used to screen samples for their overall content of PACs rather than for specific PACs.
Let us investigate the reaction mechanisms that would be involved in a situation in which an antibody is targeted to a group of antigens having multiple-antigenic sites. This model is relevant to the situation in which the antibody is designed to have a paratope targeted to only a monocyclic aromatic-or part of a monocyclic ring. Such an antibody would be capable of recognizing not only one PAC, but a family of PACs. Figure 3.8 schematically depicts such an antibody targeted to a family of PACs. The concept of multivalency for antibodies requires certain conditions. In general, antibodies are larger than antigens. Therefore, certain size and steric conditions must be fulfilled to allow more than one antibody to be attached to an antigen. This could occur for antigens with sufficiently large size or with antibodies specifically designed to have a small size or sterically favorably paratope
Table 3.1 Kinetic Expressions for Attachment of Antigen in Solution to Antibody on the Surface or of Antibody in Solution to Antigen on the Surface
Type of Antigen in solution/antibody Antibody in solution/antigen binding on surface on surface
Dual-step with lateral interactions
FIGURE 3.8 Schematic diagram of antibodies having paratopes targeted to the antigen series of polycyclic aromatic compounds.
Sadana, A. and Madugula, A., Biotechnology Progress, 9, 259-266 (1993). Reprinted with permission from Academic Press.
geometry. Of course, the combining site on the antibody should not be so large that it completely encloses the PAC (antigen). Note that steric hindrance may be particularly significant if the binding pockets are generally deep. Also, it may be challenging to design an antibody to have a PAC-combining site smaller than a PAC that would have a useful binding affinity. Another approach is to design systems consisting of parts of the antibody by cleaving and combining the appropriate paratopes.
The analysis of multivalent antigen-antibody binding is still in the initial stage. We now briefly present some possible mechanisms of multivalent antigen-antibody binding involving lateral interactions. Figure 3.9a shows the elementary steps involved in the binding of divalent antigen in solution to divalent antibody noncovalently or covalently attached to the surface. The dotted lines indicate the lateral interactions involved. Sadana and Vo-Dinh (1997) have presented the reaction scheme involved without the lateral
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