Dendrimeric bisphosphonates for multivalent protein surface binding.
A single weak-binding event is multiplied into an efficient receptor site for protein surfaces (<10(-1) to >10(6) M(-1) in buffered aqueous solution) in a biomimetic fashion. This has hitherto been done with natural host/guest pairs, but not with artificial receptors. The organic reaction presented is one of very few that enable chemists to fuse multiple ionic building blocks covalently in highly polar solution; this one-pot reaction proceeds with virtually quantitative yield. According to this concept, other building blocks with aldehyde groups can likewise be multiplied into monodisperse functional dendrimers. Small basic proteins are bound by octameric dendrimers in 1:1 or 1:2 complexes with millimolar to submicromolar affinities. The complexation event is studied independently in buffered aqueous solution by three different spectroscopic methods (PFG-LED, UV/Vis, and fluorescence). Potential new applications include recombinant protein purification through Arg tags on immobilized dendrimers and on/off switching of protein function by reversible active-site capping of enzymes.
Arendt
Markus
M
Fachbereich Chemie der Universität, Hans-Meerwein-Strasse, 35032 Marburg, Germany.
Sun
Wei
W
Thomann
Jens
J
Xie
Xiulan
X
Schrader
Thomas
T
D001665:Binding Sites; D002621:Chemistry / Q000379:methods; D045304:Cytochromes c / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry*; D004058:Diffusion; D004164:Diphosphonates / Q000737:chemistry*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D011506:Proteins / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry / Q000379:methods; D013499:Surface Properties
D050091:Dendrimers; D004164:Diphosphonates; D011506:Proteins; D011994:Recombinant Proteins; D045304:Cytochromes c