Targeting Toxins by Conjugation to Antibodies: The Effect of the Linkage Group on Biological Activity
Interest is growing in the potential use of conjugates of antibodies and toxins or their A chains as therapeutic agents. So far, convincing evidence has been presented on the in vitro efficacy and selectivity of such conjugates, but less information is available on in vivo properties . Amongst ways in which protein-protein conjugates can be made, the use of homobifunctional agents is well known; but a more elegant heterobifunctional agent has been described involving the use of a derivatized chlorambucil (CB). This introduces in sequential manner a linkage through an amide bond onto the first protein and a piperazine ring onto the second . The bonds are not subject to reduction. In another method, N-succinimidyl-3-(2-pyridyl-dithio) propionate (SPDP) is used to introduce a disulphide bridge flanked by two amide groups .
KeywordsLinkage Group Amide Group Amide Bond Chain Activity Sequential Manner
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