SOLID-PHASE SYNTHESIS AND SOME PHARMACOLOGICAL PROPERTIES OF [8-PHENYLALANINE]-OXYTOCIN

In an attempt to establish the identity of a principle designated as EOF I (elasmobranch oxytocin-like principle I), which has been isolated from the pituitary gland of the spiny dogfish (Squalus acanthias), [8-phenylalanine]-oxytocin has been synthesized and tested for some of the pharmacological activities characteristic of the neurohypophysial hormones. The synthesis was accomplished by means of the Merrifield solid-phase method as employed for the synthesis of oxytocin and glumitocin. After purification by gel filtration on Sephadex G-15, the product was obtained in 38% over-all yield. Bioassays yielded the following activities with their 95% confidence limits: rat uterus (no Mg2+), 108 (100-117) units/mg; rat uterus (+Mg2+), 366 (332-406) units/mg; fowl vasodepressor, 191 (170-214) units/mg; rabbit milk ejection, 341 (316-368) units/mg; rat vasopressor, 0.97 (0.90-1.04) units/ mg; rat antidiuretic, 1.16 (0.92-1.46) units/mg; and frog bladder activity, 1700 (1240-2360) units/mg. A comparison of these properties with those obtained for EOP I indicates that the latter is not [8-phenylalanine]-oxytocin. © 1969, American Chemical Society. All rights reserved.