Macromolecular beta-adrenergic antagonists discriminating between receptor and antibody.

Abstract

The .beta.-adrenergic antagonist, alprenolol, was attached in an irreversible manner to macromolecular dextran via side arms that differed in length. The ability of these macromolecules to bind to the .beta.-adrenergic receptor of frog erythrocytes and to catecholamine-binding antibodies raised against partially purified receptors was studied. Compared to the parent drug the potency of binding of macromolecular alprenolol to the receptor decreased about 1/10, 1/600 and 1/8000 when the length of the arm separating alprenolol from the dextran moiety was 13, 8 and 4 atoms, respectively. The binding potencies of the parent drug and of all its macromolecular derivatives for the antibody were within the same order of magnitude. Conversion of a drug to a macromolecular form may not only sustain its binding activity but may also lead to a higher selectivity. The macromolecular derivatives described here may be suitable probes for investigation of the location and of the molecular properties of the binding sites for .beta.-adrenergic drugs.