Steroidogenic activity of a peptide specified by the reversed sequence of corticotropin mRNA.
The molecular recognition theory predicts that a reversed (3'----5') reading of an mRNA should yield a peptide that is structurally and functionally similar to that specified in the 5'----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'----5', had a similar hydropathic profile to native ACTH-5'----3' but had only 30% sequence homology and eight different charge substitutions. ACTH-3'----5' specifically bound to the surface of mouse Y-1 adrenal cells and to polyclonal anti-ACTH antibody. Additionally, ACTH-3'----5' stimulated cAMP synthesis and steroidogenesis in adrenal cells. These findings show that ACTH-3'----5' mimics the corticotropic properties of native ACTH, thereby further validating the molecular recognition theory.
Clarke
B L
BL
Department of Physiology and Biophysics, University of Alabama, Birmingham 35294.
Blalock
J E
JE
D000311:Adrenal Glands / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D002417:Cattle; D002460:Cell Line; D003345:Corticosterone / Q000096:biosynthesis; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D016372:RNA, Antisense / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D018043:Receptors, Corticotropin; D011979:Receptors, Pituitary Hormone / Q000187:drug effects / Q000378:metabolism
D010455:Peptides; D016372:RNA, Antisense; D012333:RNA, Messenger; D018043:Receptors, Corticotropin; D011979:Receptors, Pituitary Hormone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone