Synthesis and some pharmacological properties of tocinoic acid and deaminotocinoic acid

Abstract

Tocinoic acid, the 20-membered cyclic disulfide ring of cysteinyltyrosylisoleucylglutaminylasparaginylcysteine, which possesses the tocin ring of oxytocin, was synthesized by the stepwise p-nitrophenyl ester method. All protecting groups of the protected intermediate Z-Cys(Bzl)-Tyr-Ile-Gln-Asn-Cys(Bzl)-ONB were removed on addition of this peptide to Na in NH3. The reduced peptide was converted to purified tocinoic acid by oxidation, followed by partition chromatography and gel filtration. Deaminotocinoic acid was synthesized by similar methods. No C-terminal carboxamide derivatives could be detected. Tocinoic acid possessed 0.2-0.3 unit/mg of oxytocic activity and no detectable avian vasodepressor activity, while deaminotocinoic acid had 3.7 ± 0.3 units/mg of oxytocic activity and no detectable avian vasodepressor activity. Deaminotocinoic acid possessed a slight inhibitory effect on the avian vasodepressor activity of synthetic oxytocin.

Analogs of oxytocin containing a pseudopeptide Leu‐Gly bond of cis and trans configuration*

“…Prolyl-leucyl-glycinamide (2 mg) was added to the solution of deaminotocinoic acid (5,19) (1.2mg) dissolved in dimethylformamide (20pL). After the addition of diphenyl phosphoryl azide (2pL) and diisopropylethylamine (2 pL) the mixture was shaken at room temperature.…”

Melanophore Stimulating Hormone: Release Inhibition by Ring Structures of Neurohypophysial Hormones

“…We have found (7) that this syn,thetic crystalline tripeptide failed to inhibit the in vitro release of MSH from either rat or frog pituitaries, whereas hypothalamic extracts of .these species were effective inhibitors of MSH release. However, we have found that tocinoic acid (8) L-CyS-L-Tyr-L-Ile-L-Gln-L-Asn-L-Cys-OH the ring of oxytocin (9), is a potent inhibitor of MSH release from the rat pars intermedia, and we have proposed that it (or a closely related structure) may be a more likely candidate as the natural MRIF in vertebrates. We now provide additional data on the MRIFlike activity of various ring compounds related to the neurohypophysial hor- The amount of MSH released into the incubation medium from isolated pituitaries or pars intermedia is determined (10) by photoreflectance methods described originally for the frog skin bioassay for MSH (11).…”