Detail of "60786-59-6"

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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

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. Lowbridge, John; Manning, Maurice; Haldar, Jaya; Sawyer, Wilbur H. (Dep. Biochem., Med. Coll. Ohio, Toledo, Ohio, USA). J. Med. Chem., 20(1), 120-3 (English) 1977. CODEN: JMCMAR. DOCUMENT TYPE: Journal CA Section: 2 (Hormone Pharmacology) Section cross-reference(s): 34 [4-Threonine,7-glycine]oxytocin [60786-59-6] and [1-(L-2-hydroxy-3-mercaptopropanoic acid),4-threonine,7-glycine]oxytocin (hydroxy[Thr4,Gly7]oxytocin) [60786-60-9] were synthesized by a combination of solid-phase and classical methods of peptide synthesis. [7-Glycine]oxytocin [19748-53-9] was prepd. from a sample of the protected nonapeptide intermediate. [7-Glycine]oxytocin had an oxytocic potency (O) of 93 units/mg and an antidiuretic potency (A) of 0.0056 units/mg. It had an O/A ratio of 16000. [4-Threonine,7-glycine]oxytocin had an oxytocic potency of 166 units/mg and antidiuretic potency of 0.002 units/mg. Its O/A ratio was 83000. Threonine substitution thus brought about a substantial enhancement in oxytocic activity and a 5-fold enhancement in O/A selectivity. Hydroxy[Thr4,Gly7]oxytocin had an oxytocic potency of 218 units/mg and an antidiuretic potency of 0.0040 units/mg. 60786-61-0 and 30134-76-0 which are cas registry numbers of substances are two of reagents here. Its O/A ratio was thus 54500. All 3 7-glycine-substituted analogs exhibited a marked sensitivity to Mg on the rat uterus assay system and in the presence of 0.5 mM Mg had oxytocic potencies in the range of 900-1000 units/mg. If these peptides exhibit enhanced oxytocic selectivity in humans, they might offer a greater margin of safety than oxytocin [50-56-6] in those clin. situations in which the latter is currently employed. .

Dose-response behavior on the isolated rat uterus of oxytocin analogs with modifications at binding sites

Dose-response behavior on the isolated rat uterus of oxytocin analogs with modifications at binding sites. Smith, Clark W.; Chan, Susanna; Walter, Roderich (Dep. Physiol. Biophys., Univ. Illinois Med. Cent., Chicago, Ill., USA). J. Pharmacol. Exp. Ther., 203(1), 120-4 (English) 1977. CODEN: JPETAB. DOCUMENT TYPE: Journal CA Section: 2 (Hormone Pharmacology) The dose-response behavior on the in vitro rat uterus of analogs of oxytocin [50-56-6] with modification at sites in the mol. which have been predicted to contribute to the binding of the peptide to the smooth muscle receptor was studied. Dose-response curves of [7-(3,4-dehydroproline)]oxytocin [61894-91-5], [7-glycine]oxytocin [19748-53-9], [7-alanine]oxytocin [58445-99-1], deamino[7-glycine]oxytocin [58445-98-0], and [4-threonine,7-glycine]oxytocin [60786-59-6] were detd. and compared with that of oxytocin. Neither the slope of the curves nor the maximal response obtained for any of the analogs differed from that obtain for the hormone. The uterotonic potencies of the analogs corresponded to the relative positions along the concn. axis of their dose-response curves and to their binding affinities. Apparently, differences in uterotonic potencies of these analogs are the result of differences in their affinity for the uterine receptor. The exptl. identification of positon 7 of neurohypophyseal peptides as a hormone-receptor binding site corroborates such a proposed role for the side chain of this residue based on earlier conformation-activity considerations.