Synthesis and [formula omitted] bioactivity of C-terminal deleted analogs of human growth hormone-releasing factor

Abstract

A series of C-terminal deleted analogs of human growth hormone-releasing factor (hGRF) with either an amidated or a free carboxylic acid C-terminus were synthesized by solid phase methodology. Their capacity to re;ease growth hormone was tested on rat anterior pituitary cells in monolayer culture. A gradual decrease of bioactivity down to 23% relative to hGRF was noted when the C-terminal amino acids were deleted to hGRF(1–34)OH. Further deletions, however, did not decrease the bioactivity because the potencies of the fragments, hGRF(1–31)NH 2, (1–30)NH 2 and (1–29)NH 2 remained at about 50% of that of hGRF. Continual deletion of residues to hGRF(1–23)NH 2, (1–22)NH 2 and (1–21)NH 2 still yielded bioactive fragments with full intrinsic activity despite very low potency. Only with the deletion down to hGRF(1–19)NH 2 did the bioactivity completely disappear. Thus, together with the data published in a previous paper (1), the minimal biologically active core of hGRF with full intrinsic activity comprises the fragment (3–21).