Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1 Synthetic analogues of oxytocin and of lysine-vasopressin with an hydroxyl group in either the L ro D configuration replacing the primary amino group have been tested for biological activity.2 [1-(L-2-Hydroxy-3-mercaptopropanoic acid)] oxytocin ([L-Hmp(1)]oxytocin) was 1.5 to 2 times more potent than oxytocin on the rat uterus in situ, the rat mammary strip and the rat mammary gland in situ and 3 times more potent on the rat isolated uterus.3 The pressor activity of [1-(L-2-hydroxy-3-mercaptopropanoic acid)-8-lysine]vasopressin ([L-Hmp(1), Lys(8)] vasopressin) was 2.2 and the antidiuretic activity 2.1 times that of lysine-vasopressin.4 The [D-Hmp(1)] analogues of oxytocin and vasopressin were much less potent than the [L-Hmp(1)] analogues.5 The responses to oxytocin and its hydroxy analogues in vivo were qualitatively indistinguishable but the pressor and antidiuretic responses to the hydroxy analogues of lysine-vasopressin were prolonged compared with those to the parent hormone.6 The hydroxy analogues of oxytocin and lysine-vasopressin were not inactivated by pregnancy plasma oxytocinase.7 The results are discussed in relation to the importance of the primary amino group for the biological activity and metabolism of the neurohypophysial hormones.
 ...
PMID:Hydroxy analogues of oxytocin and of lysine-vasopressin. 51 8

[4-Threonine, 7-glycine]oxytocin and [1-(L-2-hydroxy-3-mercaptopropanoic acid), 4-threonine, 7-glycine]oxytocin (hydroxy[Thr4, Gly7]oxytocin) were synthesized by a combination of solid-phase and classical methods of peptide synthesis. A protected octapeptide was synthesized by the solid-phase method and following ammonolysis and purification 1 + 8 couplings in solution were employed to furnish the required key nonapeptide and acyl octapeptide intermediates, respectively. [7-Glycine]oxytocin was prepared from a sample of the protected nonapeptide intermediate used in the original synthesis of this peptide. [7-Glycine]oxytocin has an oxytocic potency (O) of 93 +/- 4 units/mg and an antidiuretic potency (A) of 0.0056 +/- 0.0003 units/mg. It has an O/A ratio of 16 000. [4-Threonine, 7-glycine]oxytocin has an oxytocic potency of 166 +/- 4 units/mg and an antidiuretic potency of 0.002 +/- 0.0004 units/mg. Its O/A ratio is 83 000. Threonine substitution has thus brought about a substantial enhancement in oxytocic activity and a fivefold enhancement in O/A selectivity. Hydroxy [Thr4, Gly7]oxytocin has an oxytocic potency of 218 +/- 8 units/mg and antidiuretic potency of 0.0040 +/- 0.0005 units/mg. Its O/A ratio is thus 54 500. All three 7-glycine-substituted analogues exhibit a marked sensitivity to Mg2+ on the rat uterus assay ststem and in the presence of 0.5 mM Mg2+ had oxytocic potencies in the range of 900-1000 units/mg. Should these peptides exhibit enhanced oxytocic selectivity in humans, they might offer a greater margin of safety than oxytocin in those clinical stiuations in which the latter is currently employed.
 ...
PMID:Synthesis and some pharmacological properties of [4-threonine, 7-glycine]oxytocin, [1-(L-2-hydroxy-3-mercaptopropanoic acid), 4-threonine, 7-glycine]oxytocin (hydroxy[Thr4, Gly7]oxytocin), and [7-Glycine]oxytocin, peptides with high oxytocic-antidiuretic selectivity. 83 10

[1-(L-2-Hydroxy-3-mercaptopropanoic acid), 4-threonine]oxytocin (hydroxy[4-Thr]oxytocin) and [1-(l-2-hydroxy-3-mercaptopropanoic acid)]oxytocin (hydroxy-oxytocin) were synthesized by a combination of solid phase and classical methods of peptide synthesis. Protected octapeptides were synthesized by the solid-phase method and 1 + 8 couplings in solution were then employed to furnish the required key protected intermediates. Hydroxy[4-Thr]oxytocin has oxytocic potency as measured in the rat uterus suspended in a Mg2+-free solution, of about 4200 units/mg, eight times the potency of oxytocin, while its antidiuretic potency is approximately equal to that of oxytocin. It thus exhibits a significantly favorable oxytocic-antidiuretic sleectivity. Hydroxy-oxytocin has an oxytocic potency of approximatels 1300 units/mt, 2.5 times that of oxytocin. Threonine substitution in hydroxy-oxytocin has thus caused a significant enhancement in both oxytocic potency and selectivity. The enhancement in oxytocic potency of these two peptides relative to oxytocin and [4-Thr]oxytocin appears to correlate with their lipophilic characteristics, suggesting a significant role of lipophilicity in the interplay of oxytocin-like peptides with oxytocic receptors.
 ...
PMID:Synthesis and some pharmacological properties of [1-(L-2-hydroxy-3-mercaptopropanoic acid), 4-threonine]oxytocin (hydroxy [4-thr]oxytocin), a peptide with strikingly high oxytocic potency and of [1-(L-2-hydroxy-3-mercaptopropanoic acid)]oxytocin (hydroxy-oxytocin). 94 46