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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.

Analogs of human and rat growth hormone-releasing factor (hGRF and rGRF), related to [D-Arg 2 ]hGRF(1–29)NH 2 , were synthesized by solid phase methodology. Their capacity to inhibit growth hormone secretion stimulated by hGRF(1–44)NH 2 was tested on rat anterior pituitary cells in monolayer culture. Among the analogs of hGRF, [D-Arg 2,29 ,Arg 30 ]hGRF(1–30)NH 2 showed the highest antagonistic potency of 3.64 relative to [D-Arg 2 ]hGRF(1–29)NH 2 = 1. However, the most potent analog synthesized thus far was [N-Ac-His 1 , D-Arg 2 ,Ala 15 ]rGRF(1–29)NH 2 , which showed a relative potency of 27.7.

Fifty-four analogs of human growth hormone-releasing factor (hGRF) substituted with a single D-amino acid were synthesized by solid phase methodology. Their capacity to release growth hormone was tested on rat anterior pituitary cells in monolayer culture. Among the series of 28 analogs, which had the amino acid at each position of hGRF (1-29)NH2, except glycine at position 15, substituted by the corresponding D-isomer, [D-Ala2]-, [D-Asp3]-, [D-Asn8]-, [D-Tyr10]-, [D-Asp25]-, [D-Met27]-, [D-Ser28]-, and [D-Arg29]hGRF(1-29)NH2 were as potent as hGRF(1-29)NH2, while [D-Ile5]-, [D-Phe6]-, [D-Thr7]-, and [D-Val13]hGRF(1-29)NH2 showed quite low potencies. Effects of substitution with other D-amino acids in positions 2,3,8,9,10 and 11 were also studied. In most cases, the resulting analogs showed decreased potency, but still retained high intrinsic activity. Only [D-Arg2]hGRF(1-29)NH2 showed very low intrinsic activity and some antagonistic property.