Influence of azide incorporation on binding affinity by small papain inhibitors.
Basic Information
ID: ALA3351912
Journal: Bioorg Med Chem
Title: Influence of azide incorporation on binding affinity by small papain inhibitors.
Authors: Wammes AE, Hendriks TG, Amatdjais-Groenen HI, Wijdeven MA, van Hest JC, van Delft FL, Ritschel T, Rutjes FP.
Abstract: In order to develop affinity-based biosensor platforms, appropriate ligands with a functional handle for immobilization onto a biosensor surface are required. To this end, a library of papain inhibitors was designed and synthesized, containing different azide linkers for subsequent immobilization by 'click' chemistry, in this particular case by copper-free, strain-promoted azide-alkyne cycloaddition (SPAAC). Furthermore, a molecular docking study was performed to obtain a better insight as to at which position such azide handles could be tolerated without affecting binding affinity. Although the azide moiety is small, in some cases its introduction strongly influenced the binding affinity. For one class of inhibitors a swapped binding mode was proposed to explain the results. In addition, a specific site for linker introduction was identified, which did not significantly affect the binding affinity.
CiteXplore: 24972724
DOI: 10.1016/j.bmc.2014.06.001
Patent ID: ┄