Design and biological activity of analogs of growth hormone releasing factor with potential amphiphilic helical carboxyl termini.

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.

Curious structure in “canonical” alanine-based peptides

“…The amphiphilic regions may induce p helicity to bind with the surface. Studies of model peptides suggest that such arrangements may occur in b-endorphin, 57-59 melittin, growth hormone releasing factor, 60,61 and in analogues of a vasoactive intestinal peptide. 62 In a designed sequence, i,i15 spacing of interacting residues could be used to encourage such a structure.…”

Atrazine Binds to the Growth Hormone–Releasing Hormone Receptor and Affects Growth Hormone Gene Expression

“…Previous studies have shown that GHRF binds to GHRHR and up-regulates the expression of the GH gene in healthy human and rat pituitary cells (Bloch et al 1983; Montero et al 2000; Thorner et al 1983) with an optimal range of 1–3 μg/kg body weight in vivo and 0.1–10 nM in vitro (Thorner et al 1983; Velicelebi et al 1986). Serum levels of PRL and LH were not increased after administration of human GHRF at 1 μg/kg body weight (Thorner et al 1983).…”

Synthetic biology

“…Proteins are built from secondary structure units, including the α helix and the β strand 60 . This gave rise to the idea that such secondary structural elements might serve as interchangeable parts to support protein design 61 .…”