Macromolecular beta-adrenergic antagonists discriminating between receptor and antibody.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Pitha, J; Zjawiony, J; Lefkowitz, RJ; Caron, MG

Published Date

  • April 1980

Published In

Volume / Issue

  • 77 / 4

Start / End Page

  • 2219 - 2223

PubMed ID

  • 6154947

Pubmed Central ID

  • 6154947

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.77.4.2219


  • eng

Conference Location

  • United States