Conformational behavior of fragments of adrenocorticotropin and their antisense peptides determined by NMR spectroscopy and CD spectropolarimetry.

An 'antisense' peptide ('HTCA'), whose sequence was generated by reading the antisense RNA sequence corresponding to ACTH (1-24) was shown to bind ACTH (1-24) with a Kd of 0.3 nM in a solid-matrix binding assay [( 1986) Biochem. J. 234, 679 683]. Two-dimensional NMR spectra were used to examine the conformational behavior in methanol and in water solution of two fragments of adrenocorticotropin, ACTH(1-24) and ACTH (1-13), as well as their antisense peptides, HTCA and HTCA(12-24). The conformations are extended chains in these solutions, both as isolated molecules and when mixed with their antisense complements. The Kd values are greater than 1 mM.