An Enzyme-Labile Linker Group for Organic Syntheses on Solid Supports

Abstract

Lipases and esterases can be used to fragment the 4-acetyloxybenzyloxy group used as a linker for organic synthesis on solid supports. (A support-bound compound is shown on the right; the enzyme-labile bond is marked with an arrow.) This enzyme-initiated fragmentation proceeds under very mild conditions (pH 6-7, room temperature), and the compounds of interest (amines, alcohols, carboxylic acids; X=NH, O, CR ) constructed by combinatorial chemistry can be released with complete selectivity.

Development of a sensitive long-wavelength fluorogenic probe for nitroreductase: A new fluorimetric indictor for analyte determination by dehydrogenase-coupled biosensors

“…Recently, we reported the generation of a new long-wavelength latent fluorophore for use in monitoring salicylate hydroxylase activities with a fluorogenic coumarin-releasing mechanism based on the 1,6-rearrangementelimination reaction (Huang et al, 2010). The latter reaction has been utilized to release drugs from prodrugs (Haba et al, 2005;Flader et al, 2000), in the selective cleavage of peptides from an enzyme-labile linker during solid phase synthesis (Sauerbrei et al, 1998), and off-on fluorescence mechanism of a hydrogen peroxidesensitive latent fluorophore (Lo and Chu, 2003). We hypothesized that the same fluorescence releasing mechanism could be adapted to the design a latent fluorophore for monitoring NTR activity.…”

Nucleophile Cleavable Linker Units

“…Effective silicon based linkers which are stable to base only, yet cleaved by fluoride ion, have been described by Chao [58] and Ramage, [59] but they limit the use of silyl protecting groups in solid-phase synthesis (SPS), particularly for carbohydrate manipulation. Other carboxy linkers, requiring mild photochemical, [60] enzymatic [61] or palladium(0) [62] cleavage conditions to release the product are also available and have specific stabilities and applications. Further methodology, which has additional advantages, now offers the opportunity to extend the range of compound types amenable to SPS.…”

Enhancement of the enzymatic digestibility of sugarcane bagasse by steam pretreatment impregnated with hydrogen peroxide

“…1) because of the external PEG chains, whereas the hydrophobic PS core makes them able to swell in organic solvents also. Despite some positive results being reported for the use of lipases (30–40 kDa),16 the presence of DVB as cross‐linking agent (1–2%) creates limitations with regard to their use in aqueous solution and enzymatic catalysis 17–22…”

“…Specific linkers that present specific sites for lipase recognition have been also designed. A 4‐acyloxy‐3‐carbobenzyloxy moiety is specifically recognised by a specific lipase, generating a phenolate that breaks up to give a quinine methide and releases the desired target compound 16…”