Noncleavable cross-linkers

Figure 129 DSG is a noncleavable cross-linker that can react with two amine-containing molecules to form amide bonds.

The method for the preparation of immunotoxins with SMPB is identical to that used for MBS (above). Since the thioether bonds formed with sulfhydryl-containing molecules are noncleavable, A-chain isolates or single-chain toxin molecules cannot be conjugated with antibodies with retention of cytotoxicity. Only intact A—B toxin molecules may be used with this cross-linker, since the A chain still is capable of being reductively released from the complex. 

Finally, the small amine-reactive and photoreactive cross-linker NHS-ASA (Chapter 5, Section 3.1) can be iodinated to provide a noncleavable radioactive conjugate. 

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