Premium
Selectivity of Competitive Multivalent Interactions at Interfaces
Author(s) -
André Thomas,
Reichel Annett,
Wiesmüller KarlHeinz,
Tampé Robert,
Piehler Jacob,
Brock Roland
Publication year - 2009
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200900001
Subject(s) - nitrilotriacetic acid , chemistry , selectivity , ligand (biochemistry) , chelation , hexa , combinatorial chemistry , affinities , binding selectivity , molecular recognition , binding affinities , binding site , fluorescence , biophysics , stereochemistry , biochemistry , receptor , molecule , organic chemistry , physics , quantum mechanics , biology , catalysis
The development of synthetic, low‐molecular‐weight ligand receptor systems for the selective control of biomolecular interactions remains a major challenge. Binding of oligohistidine peptides to chelators containing Ni 2+ ‐loaded nitrilotriacetic acid (NTA) moieties is one of the most widely used and best‐characterised recognition systems. Recognition units containing multiple NTA moieties (multivalent chelator headgroups, MCHs) recognise oligohistidines with substantially increased binding affinities. Different multivalencies both at the level of the MCH and at that of the oligohistidine ligand provide a powerful means to vary the affinity of the interaction systematically. Here we have explored the selectivity for the binding of different oligohistidines to immobilised MCH. Using microarrays of mono‐, bis‐, tris‐ and tetrakis‐NTA chelators spotted at different surface densities, we explored the ability of these binders to discriminate fluorescently labelled hexa‐ and decahistidine peptides. When hexa‐ and decahistidine were tested alone, the discrimination of ligands showed little dependence either on the nature or on the density of the chelator. In contrast, coincubation of both peptides decreased the affinity of hexahistidine, increased the affinity of decahistidine, and made the binding of decahistidine highly dependent on MCH density. Kinetic binding assays by dual‐colour total internal reflection fluorescence spectroscopy revealed active exchange of His 6 by His 10 and confirmed the high selectivity towards His 10 . Our results establish the key role of surface multivalency for the selectivity of multivalent interactions at interfaces.