CDRs

SynaHoy Corp., Blackman Uhler Chemical Division CDR Pigments and Dispersions Ciba-Geigy Corp. 

The variable domains associate in a strikingly different manner. It is obvious from Figure 15.11 that if they were associated in the same way as the constant domains, via the four-stranded p sheets, the CDR loops, which are linked mainly to the five-stranded p sheet, would be too far apart on the outside of each domain to contribute jointly to the antigen-binding site. Thus in the variable domains the five-stranded p sheets form the domain-domain interaction area (Figure 15.11). Furthermore, the relative orientation of the p strands in the two domains is closer to parallel than in the constant domains and the curvature of the five-stranded p sheets is such that they do not pack... 

The shape of the interaction area between lysozyme and the CDR loops of the antibody is easily distinguished from the hapten-binding crevice. The interaction extends over a large area with maximum dimensions of about 20 X 30 A (Figure 15.15). The interaction surface is irregular but relatively flat, with small protuberances and depressions that are complementary in the antigen and the antibody. Residues from all six CDR loops contribute to the... 

The CDR loops assume only a limited range of conformations, except for the heavy chain CDR3... 

The VoJa and VpDpJp regions correspond to the CDR loops. Nucleotides can also be added or deleted from the junctions, adding further amino acid sequence diversity. 

Figure 15.22 T-cell receptor stucture shown as a ribbon diagram. The anbgen-binding site is formed by CDR loops (labeled 1 to 3) from the Va and Vp domain, as for antibodies.

Figure 17.2 An example of prediction of the conformations of three CDR regions of a monoclonal antibody (top row) compared with the unrefined x-ray structure (bottom row). LI and L2 are CDR regions of the light chain, and HI is from the heavy chain. The amino acid sequences of the loop regions were modeled by comparison with the sequences of loop regions selected from a database of known antibody structures. The three-dimensional structure of two of the loop regions, LI and L2, were in good agreement with the preliminary x-ray structure, whereas HI was not. However, during later refinement of the x-ray structure errors were found in the conformations of HI, and in the refined x-ray structure this loop was found to agree with the predicted conformations. In fact, all six loop conformations were correctly predicted in this case. (From C. Chothia et al.. Science 233 755-758, 1986.)...

List of researchers in the field of zeolites (including URLs and e-mail-adresses). Subfield Catalysis, ion-exchange and separation, http //w w w. tn. utwente. nl/cdr/S taff/Haral. 

An elegant synthesis of (5f(, 65, 8/f -6-( C(-hytltQxyethyl -2-rhytltQxymethyl penem-3-cdr-boxylic acid has been accomplished by the strategy based on the Michael adthdon and Nef reacdon CScheme 4.9)/ ... 

A number of chimerized, humanized, and one human mAb have now been approved for therapeutic use in humans in the treatment of autoimmunity, malignancy, infection and cardiovascular disease (Table 1). Some of the currently licensed mAb will be discussed here. A much larger number of mAb are currently being evaluated in Phase I, II and III trials. In general, chimeric, humanized and human mAb are very well tolerated with few side effects. Chimeric or humanized mAb still have the potential to evoke host immune response to the variable domains or CDRs of the antibody so-called HACA (human anti-chimeric antibody) or HAHA (human anti-human antibody) responses, although these responses are uncommon. Short-lived and occasionally severe infusion-related acute hypersensitivity reactions such as fever, skin itching, shivering, respiratory compromise and low blood pressure sometimes occur-. Such effects may... 

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