Macromolecular beta-adrenergic antagonists discriminating between receptor and antibody.
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. In contrast, the binding potencies of the parent drug and of all its macromolecular derivatives for the antibody were within the same order of magnitude. Thus, conversion of a drug to a macromolecular form may not only sustain its binding activity but may also lead in 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.
D000526:Alprenolol / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism; D000906:Antibodies; D001665:Binding Sites; D001666:Binding Sites, Antibody; D003911:Dextrans; D007700:Kinetics; D008970:Molecular Weight; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000906:Antibodies; D003911:Dextrans; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D000526:Alprenolol