THE CHEMICAL SYNTHESIS OF RAT RELAXIN AND THE UNEXPECTEDLY HIGH POTENCY OF THE SYNTHETIC HORMONE IN THE MOUSE

Rat relaxin, as isolated from ovaries, has been described in the liter ature as a low potency hormone in the mouse symphysis pubis assay. Sea rching for an explanation, a helix-breaking glycine residue in the B c hain seemed to be the most auspicious perturbation. Rat relaxin was ch emically synthesized and analyzed by reverse-phase high performance li quid chromatography, amino acid composition, mass spectrometry and cir cular dichroic spectroscopy. Analogs of rat relaxin were synthesized e ither with aspartic acid in place of the helix-breaking glycine residu e in the receptor-binding region of the B chain or with Asp-Leu-Val in stead of Gly-Tyr-Val at positions B14-B16. In receptor-binding assays [B14D, B15L, B16V]relaxin was a better ligand than rat relaxin, wherea s the [B14D]relaxin was less potent. In the mouse symphysis pubis assa y, both analogs were less potent than unmodified rat relaxin, but the [B14D, B15L, B16V]relaxin was better than [B14D]relaxin. In contrast t o previous reports on native rat relaxin, the chemically synthesized r at relaxin Droved to be as active as human and porcine relaxin with re spect to the standard mouse assay system. Glycine, which is considered to be a perturbator in an a helix, is not only tolerated in the B14 p osition but is required for full biological potency.