Background to the AmLinker™

AmLinker™ incorporates a pH-dependent moiety that enables its non-destructive quantification, even when covalently attached to a wide range of proteins.  Additionally, formation of a second linkage bond between the AmLinker™ decorated carrier and a range of ligands, results in a second reversible absorbance change; enabling the forward (ligand loading) and reverse (ligand release for analysis) reactions of ligand loading to be monitored in situ and quantified in real-time. 

Incorporation of a quaternary amine moiety into AmLinker™ increase the relative solubility of protein conjugates, enabling significantly higher loading of proteins with linker and subsequent ligands, whilst retaining aqueous solubility, when compared to standard methods.

PubMed link to AmLinker™ paper: here

AmLinker™ permits the chemoselective linking of molecules (X) to other molecules (e.g. proteins or solid surfaces (Y)) in order to provide screening and diagnostic tools as part of the drug discovery process.  A chemical switch (Z) can also be incorporated permitting the controlled release of “X” from “Y”

                                              X–Z-LINKER -Y

The technology has wide applications in diverse areas including synthetic vaccines (e.g. X is an antigen, Y is a carrier protein), medical devices (e.g. X is an anticoagulant, Y is a stent), diagnostics (e.g. X is an antibody, Y is a substrate), targeted drug delivery (e.g. X is cancer directed antibody, Y is cytotoxic agent), chromatography (e.g. X is an affinity ligand, Y is a chromatography column resin), screening systems (e.g. X is an ion channel, Y is a 96 well plate or a bead), etc.

The linking moiety allows attachment of the biologically active molecule without changes in conformational integrity (important for large molecules) solubility or orientation so that very high loading can be achieved and biological integrity is not compromised.  The technology has been developed to a proof of concept stage with a synthetic vaccine for which very high antigen loading was achieved. This gave an improved antibody titre compared with that from a conventional vaccine.

AmLinker™ is also emergent in the field of glycomics. Amura has discovered and patented a modular method for binding carbohydrate moieties via AmLinker™ to natural and synthetic polymers.

PubMed link to AmLinker™ paper for preparation of glycoconjugate: here