Self-immolative linker

FIGURE 5.1 Graphical structure of a tripartite prodrug with self-immolative linker. (See the color version of this figure in Color Plates section.)... 

FIGURE 5.1 Graphical structure of a tripartite prodrug with self-immolative linker. 

Figure 7 A PARACEST self-immolative contrast agent the enzyme specifically reacts with the substrate leading to the spontaneous elimination of the self-immolative linker.

Blencowe, C. A., Russell, A.T., Greco, E, Hayes, W. and Thornthwaite, D. W. (2011). Self-immolative linkers in polymeric delivery systems. Polymer Chemistry, 2, 773-790. 

Michael substrate of antibody 38C2 was attached to the adaptor platform through a self-immolative linker of adequate length, to avoid steric hindrances accompanying the complex structure of the doxorubicin (DOX) molecule (Scheme 18) or the campthotedn (CPT) (Scheme 19). 

The linker used to attach the antibody and cytotoxic agent was greatly under-appreciated in early ADC research, but has become a central focus for more recent conjugate research efforts. The broadest activity for ADCs has been obtained with cleavable linkers that contain disulfides, peptides, or acyl hydrazones that, when properly chosen, all have acceptable stability in circulation but are successfully cleaved under conditions encountered intra-cellularly. The peptides and hydrazones are most likely cleaved in the lysosomes while most disulfides are believed to be reduced in the cytosol. This approach has the additional advantage that the species released can be predicted, controlled, and modified, albeit within the limits of the linker technology. All of these approaches can be used in a self-immolative mode that cleaves off any residual linker to release a specific desired derivative in un-derivatized form. ... 

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