Solid phase synthesis of human growth hormone-releasing factor analogs containing a bicyclic beta-turn dipeptide.

Three analogs derived from the N-terminal 29-residue fragment of human growth hormone-releasing factor (hGRF) which contained a bicyclic beta-turn dipeptide (BTD) at 7-8, 8-9, and 9-10 positions were synthesized by solid phase methodology to ascertain if the beta-turns are important for the biological activity of hGRF and also to show the applicability of the BTD unit to solid phase synthesis. All three analogs were obtained in good yield and purity indicating that the BTD unit can be used in the usual condition of solid phase synthesis. The capacity of these analogs to release growth hormone (GH) was tested in an in vitro bioassay using rat anterior pituitary cells. All three BTD-containing analogs showed the same maximal GH secretion with parallel dose-response curves to that of hGRF(1-29)NH2, except their relative potencies were very low.