Synthetic analogs of growth hormone-releasing factor with antagonistic activity in vitro

Analogs of human and rat growth hormone-releasing factor (hGRF and rGRF), related to [D-Arg2]hGRF(1-29)NH2, were synthesized by solid phase methodology. Their capacity to inhibit growth hormone secretion stimulated by hGRF(1-44)NH2 was tested on rat anterior pituitary cells in monolayer culture. Among the analogs of hGRF, [D-Arg2,29,Arg30]hGRF(1-30)NH2 showed the highest antagonistic potency of 3.64 relative to [D-Arg2]hGRF(1-29)NH2 = 1. However, the most potent analog synthesized thus far was [N-Ac-His1,D-Arg2,Ala15]rGRF(1-29)NH2, which showed a relative potency of 27.7.