The Synthesis and Some Pharmacological Properties of Tocinoic Acid and Deaminotocinoic Acid1a,b

Victor J. Hruby; Clark W. Smith; David K. Linn; Martha F. Ferger; Vincent du Vigneaud

doi:10.1021/ja00770a052

The Synthesis and Some Pharmacological Properties of Tocinoic Acid and Deaminotocinoic Acid1a,b

Victor J. Hruby, Clark W. Smith, David K. Linn, Martha F. Ferger, Vincent du Vigneaud

Chemistry and Biochemistry

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Tocinoic acid, the 20-membered cyclic disulfide ring of cysteinyltyrosylisoleucylglutaminylasparaginyl-cysteine, 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.

Original language	English (US)
Pages (from-to)	5478-5480
Number of pages	3
Journal	Journal of the American Chemical Society
Volume	94
Issue number	15
DOIs	https://doi.org/10.1021/ja00770a052
State	Published - Jul 1 1972

ASJC Scopus subject areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

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title = "The Synthesis and Some Pharmacological Properties of Tocinoic Acid and Deaminotocinoic Acid1a,b",

abstract = "Tocinoic acid, the 20-membered cyclic disulfide ring of cysteinyltyrosylisoleucylglutaminylasparaginyl-cysteine, 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.",

author = "Hruby, {Victor J.} and Smith, {Clark W.} and Linn, {David K.} and Ferger, {Martha F.} and {du Vigneaud}, Vincent",

year = "1972",

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AU - Hruby, Victor J.

AU - Smith, Clark W.

AU - Linn, David K.

AU - Ferger, Martha F.

AU - du Vigneaud, Vincent

PY - 1972/7/1

Y1 - 1972/7/1

N2 - Tocinoic acid, the 20-membered cyclic disulfide ring of cysteinyltyrosylisoleucylglutaminylasparaginyl-cysteine, 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.

AB - Tocinoic acid, the 20-membered cyclic disulfide ring of cysteinyltyrosylisoleucylglutaminylasparaginyl-cysteine, 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.

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The Synthesis and Some Pharmacological Properties of Tocinoic Acid and Deaminotocinoic Acid1a,b

Abstract

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