A molecular recognition hypothesis for nonpeptides: Na+ K+ ATPase and endogenous digitalis-like peptides |
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Authors: | J J Mulchahey G Nagy J D Neill |
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Institution: | (1) Department of Physiology and Biophysics, 812 MCML Building, 1918 University Boulevard, University of Alabama at Birmingham, Birmingham (Alabama 35294-0005, USA), Fax +1 205 975 7679, e-mail: Neill@uab.edu, US |
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Abstract: | The molecular recognition hypothesis for peptides is that binding sites of ligands and their receptors are encoded by short,
complementary segments of DNA. A corollary hypothesis for nonpeptide ligands posited here is that peptide replicas may be
encoded by the DNA segment complementary to the receptor binding sites for nonpeptides. This corollary was tested for digitalis,
a family of cardiotonic and natriuretic steroids including ouabain. A hexapeptide (ouabain-like peptide, OLP) complementary
to a ouabain binding site on sodium/potassium dependent adenosine triphosphatase (Na+ K+ ATPase) exhibited activity in a digitalis bioassay. Antisera to the complementary peptide (OLP) stained the neurohypophysis
in an immunocytochemical procedure. The complementary peptide was found to share an identical 4-amino acid region with the
39-amino acid glycopeptide moiety of the vasopressin-neurophysin precursor. This glycopeptide was isolated from pituitary
extracts; it exhibited digitalis-like activity in the submicromolar range and cross-reacted with complementary peptide antibodies.
Another digitalis-like substance with high activity also was detected in the extracts. These results demonstrate that the
vasopressin-neurophysin glycopeptide has digitalis-like activity. Moreover, the findings are consistent with the hypothesis
that peptide mimetics of nonpeptides are encoded in the genome.
Received 23 November 1998; received after revision 18 January 1999; accepted 19 February 1999 |
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Keywords: | , Molecular recognition, ouabain, Na+ K+ ATPase, vasopressin-neurophysin, glycopeptide 1-39, complementary peptide,,,,,,ouabain-like peptide, |
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