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. 1980 Apr;77(4):2219–2223. doi: 10.1073/pnas.77.4.2219

Macromolecular beta-adrenergic antagonists discriminating between receptor and antibody.

J Pitha, J Zjawiony, R J Lefkowitz, M G Caron
PMCID: PMC348684  PMID: 6154947

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. 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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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