Self-immolative linkers in polymeric delivery systems

Abstract

There has been significant interest in the methodologies of controlled release for a diverse range of applications spanning drug delivery, biological and chemical sensors, and diagnostics. The advancement in novel substrate-polymer coupling moieties has led to the discovery of selfimmolative linkers. This new class of linker has gained popularity in recent years in polymeric release technology as a result of stable bond formation between protecting-and leaving groups, which becomes labile upon activation, leading to the rapid disassembly of the parent polymer. This ability has prompted numerous studies into the design and development of self-immolative linkers and the kinetics surrounding their disassembly. This review details the main concepts that underpin self-immolative linker technologies that feature in polymeric or dendritic conjugate systems and outlines the chemistries of amplified self-immolative elimination. 65 For the purpose of clarity, a colour scheme has been adopted to highlight trigger (blue), self-immolative linker (green) and reporter (red) moieties.

Versatile approach to α-alkoxy carbamate synthesis and stimulus-responsive alcohol release

“…1 Carbamates have frequently been used to release amines in these processes due to the diverse array of stimuli that can be employed for the decomposition step. We have initiated a program by which α-alkoxy carbamate cleavage can serve to release alcohols in response to externally-applied stimuli, as shown in Scheme 1.…”

Peptide-Based Polymer Therapeutics

“…For instance, there are specific peptidyl sequences recognised by enzymes present at the disease site, i.e., the tumour-associated protease legumain [189] or the well-known matrix-metalloproteinases (MMP) [190], which are associated enzymes with a number of types of cancer and other diseases that are essential in disease progression. Creativity in the field has built self-immolative linkers [191] or bioresponsive coiled-coil peptide linkers [192] with promising applications.…”

Investigation of self-immolative linkers in the design of hydrogen peroxide activated metalloprotein inhibitors

“…The use of self-immolative linkers has become increasingly popular in drug development, molecular sensors, and polymeric delivery systems. 1, 19–21 Linkers that undergo self-immolative elimination upon removal of the protecting group can release an active species through a 1,6-benzyl elimination (Fig. 1).…”