TY - JOUR
T1 - Influence of azide incorporation on binding affinity by small papain inhibitors
AU - Wammes, A.E.M.
AU - Hendriks, T.G.
AU - Amatdjais-Groenen, H.I.V.
AU - Wijdeven, M.A.
AU - van Hest, J.C.M.
AU - Van Delft, F.L.
AU - Ritschel, T.
AU - Rutjes, F.P.J.T.
PY - 2014/10/15
Y1 - 2014/10/15
N2 - 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.
AB - 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.
KW - Azides
KW - Biosensors
KW - Docking study
KW - Papain inhibitors
KW - Strain-promoted cycloaddition
UR - http://www.scopus.com/inward/record.url?scp=84908508864&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2014.06.001
DO - 10.1016/j.bmc.2014.06.001
M3 - Article
C2 - 24972724
AN - SCOPUS:84908508864
SN - 0968-0896
VL - 22
SP - 5593
EP - 5603
JO - Bioorganic & Medicinal Chemistry
JF - Bioorganic & Medicinal Chemistry
IS - 20
ER -