The present invention relates to artificial receptors on scaffolds, methods of and compositions for making them, and methods of using them. Each artificial receptor includes a plurality of building block compounds coupled to a scaffold. In an embodiment, at least one of the building blocks includes a tether moiety. The tether can provide spacing or distance between the recognition element and the scaffold to which the building block is immobilized. A tether moiety can have any of a variety of characteristics or properties including flexibility, rigidity or stiffness, ability to bond to another tether moiety, and the like.