Macromolecular beta-adrenergic antagonists discriminating between receptor and antibody.
Published
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
Language
- eng
Conference Location
- United States