A comparative study of the self-immolation of para-aminobenzylalcohol and hemithioaminal-based linkers in the context of protease-sensitive fluorogenic probes

Abstract

This study focuses on the disassembly-behavior of self-immolative pro-fluorescent linkers under physiological conditions and through an enzyme-initiated domino reaction. The targeted linkers are based on para-aminobenzylalcohol (PABA) or hemithioaminal derivatives of para-carboxybenzaldehyde or glyoxilic acid. We found that a fine tuning of the kinetic properties could be obtained through the modulation of the linker structure, giving either a fast signal response or free-adaptable systems suitable for the design of protease-sensitive fluorogenic probes or prodrug systems.

Synthesis and Biological Evaluation of RGD Peptidomimetic–Paclitaxel Conjugates Bearing Lysosomally Cleavable Linkers

“…cyclo[DKP-RGD]-CH 2 NH 2 (2), [19] Fmoc-Val-Ala-N-[4-(hydroxymethyl)-phenyl] (10 a), [30] and N-(Boc)-N,N'-dimethylethylenediamine (17) [25] were prepared according to the literature procedures, and their analytical data were in agreement with those already published. The synthetic procedures for the preparation of compounds 7 and 8 are included in the Supporting Information, along with the 1 H NMR and 13 C NMR spectra, the HPLC traces of the final RGD-PTX conjugates, and the procedures for the evaluation of the cellular expression of a v b 3 integrin.…”

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

“…Recently, this ether linkage was utilized in studies on ROS-sensitive luciferase probes 24 and protease-sensitive fluorophores. 22 Nonetheless, there are essentially no studies on the generality and utility of this promising linking strategy. This report investigates the scope of this ether-connected, self-immolative proinhibitor strategy with a variety of functional groups and MBGs.…”

Magnetogenese unter physiologischen Bedingungen mit molekularen Sonden, die auf (bio‐)chemische Analyten ansprechen

“…[15][16][17] und in jüngerer Vergangenheit auch für aktivierbare Fluoreszenzsonden vorgeschlagen wurden. [18][19][20][21] Was vielmehr bençtigt wird, ist ein System, das beträchtliche potentielle Energie speichern kann (Sprungfeder-artig), die zur Überwindung des Chelateffekts zur Verfügung steht, sobald die Peripherie des Komplexes durch den gewünschten Stimulus chemisch verändert wird. Die Herausforderung besteht darin, diesen hohen Energieinhalt zu erreichen, ohne a) die Mçglichkeit zu verlieren, diesen Energieinhalt durch einen blockierenden Substituenten (die mit dem Analyten reagierende Gruppe) zu steuern, und b) ohne damit die Chancen auf eine zunächst robuste Sonde zu verringern.…”