Super-active analogs of growth hormone-releasing factor (1–29)-amide

Human pancreatic growth hormone releasing factor (1–29)-amide [hpGRF (1–29)-NH 2] and the following analogs: [D-Tyr-1]-hpGRF (1–29)-NH 2, [D-Ala-2]-hpGRF (1–29)-NH 2, [D-Asp-3]-hpGRF (1–29)-NH 2, and [N-Ac-Tyr-1]-hpGRF (1–29)-NH 2 were synthesized using solid phase methodology and tested for their ability to stimulate growth hormone (GH) secretion in the rat and the pig in vivo. [D-Ala-2]-hpGRF (1–29)-NH 2 was approximately 50 times more potent than the parent molecule in eliciting GH secretion in the rat. The other analogs were less active, but all were more potent than the 1–29 amide in the rat. [D-Tyr-1]-hpGRF (1–29)-NH 2 was 10 times more potent, [D-Asp-3]-hpGRF (1–29)-NH 2 7 times more potent, and the acetylated molecule approximately 12 times more potent than hpGRF (1–29)-NH 2.