Antisense Peptides: Tools for Receptor Isolation? Lack of Antisense Msh and Acth to Interact with their Sense Peptides and to Induce Receptor-Specific Antibodies

Abstract

The use of antisense peptides for receptor isolation as proposed by Blalock and his colleages (e.g. TIBTECH 8, 140–144, 1990) was tested for human ACTH as well as α- and β-MSH. We synthesized the corresponding antisense peptides HTCA_h, HSM-α and HSM-β and analyzed them for specific interaction with the sense peptides using several types of binding assay and bioassay. Similarly HTCA_h antibodies were tested for binding to ACTH receptors and ACTH antibodies. All these experiments were negative, i.e. there was no specific interaction between sense and antisense peptides nor between the corresponding antibodies. Receptor binding of the sense peptides was not affected by the antisense peptides or HTCA_h antibodies. Unexpectedly, HTCA_h but not HSM-α or HSM-β was a weak MSH agonist acting through a site independent of the MSH receptor. A detailed analysis of the concept of antisense peptides revealed that the theoretical background of the hypothesis of the ‘molecular recognition theory’ is rather weak, explaining the failure of various attempts to obtain specific receptor antibodies.