Abstract
A 29-amino acid analog of growth hormone releasing factor (GHRF) was designed in which the sequence of the first six amino acids at the amino terminus was maintained while the postulated amphiphilic helical structure in the remainder of the molecule was optimized. The amino acid sequence of the analog differed from that of the first 29 residues of human GHRF by 13 residues. The peptide was synthesized by the solid-phase procedure in amide and free acid forms, both of which were tested for biological activity. When assayed for the ability to stimulate growth hormone secretion in primary cultures of rat anterior pituitary cells, the amide analog was 1.57 times as potent as GHRF-(1-40)-OH, which was used as the standard for comparison, while the free acid form was 1/6th as potent in the same assay. The two forms of the analog were also tested for stimulation of cAMP formation; they exhibited relative potencies similar to those observed for growth hormone secretion. The high activity of the analog provides good evidence for the importance of an amphiphilic helical structure in the carboxyl-terminal portion of the GHRF molecule.
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