Steroidogenic activity of a peptide specified by the reversed sequence of corticotropin mRNA.

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Abstract
The molecular recognition theory predicts that a reversed (3'' .fwdarw. 5'') reading of an mRNA should yield a peptide that is structurally and functionally similar to that specified in the 5'' .fwdarw. 3'' direction. We tested this idea by synthesizing a corticotropin (ACTH) analogue using a reverse reading of bovine mRNA for ACTH (1-24). This peptide, designated ACTH-3'' .fwdarw. 5'', had a similar hydopathic profile to native ACTH-5'' .fwdarw. 3'' but had only 30% sequence homology and eight different charge substitutions. ACTH 3'' .fwdarw. 5'' specifically bound to the surface of mouse Y-1 adrenal cells and to polyclonal anti-ACTH antibody. Additionally, ACTH-3'' .fwdarw. 5'' stimulated cAMP synthesis and steroidogenesis in adrenal cells. These findings show that ACTH-3'' .fwdarw. 5'' mimics the corticotropic properties of native ACTH, thereby further validating the molecular recognition theory.