pituitrin and deaminooxytocin

We present the time-resolved phosphorescence of oxytocin, two oxytocin derivatives, vasopressin and a series of compounds that serve as models for free tyrosine. One of the oxytocin derivatives, desaminodicarbaoxytocin, has the disulfide bridge replaced by an ethylene bridge, and lacks the N-terminus. Similar to the reported fluorescence decays of tyrosine in these peptides, the phosphorescence decays generally are not single exponentials, but can be fit as biexponentials. The decay times for the oxytocin peptides are shorter than for desaminodicarbaoxytocin or the model compounds, and this we attribute to enhanced spin-orbit coupling due to the presence of sulfur. We measured the phosphorescence decay of the model cyclic pentapeptide that contains tyrosine and compared it to that observed for the same cyclic pentapeptide in which tyrosine is replaced by tryptophan. We also report the phosphorescence of 2-tryptophan-oxytocin, and deamino-2-tryptophan-oxytocin in which biexponential phosphorescence decay is also observed.

Topics: Disulfides; Hydrogen-Ion Concentration; Models, Statistical; Oxytocin; Peptides; Phenol; Protein Conformation; Protein Structure, Tertiary; Spectrometry, Fluorescence; Time Factors; Tryptophan; Tyrosine; Vasopressins

With the aim of developing inhibitors of vasopressin- and oxytocin-induced uterine activity, 17 analogues of 1-deamino-oxytocin were synthesized by the solid-phase method. Modifications were made at positions 2, O-methyltyrosine (Tyr(OMe] and O-ethyltyrosine (Tyr(OEt],D-Tyr,D-Tyr(OEt),D-Trp; 4, Val,Thr and 8, Orn,Cit,Arg,D-Arg. The analogues were tested for antiuterotonic activity in vitro and in vivo in the rat and in vitro on myometrial strips from non-pregnant women and pregnant women at term. Their selectivity was also investigated in blood pressure and antidiuretic bioassays in rats. Results were compared with those from an original antiuterotonic analogue 1-deamino-2-Tyr(OEt)-oxytocin (d(OEt)-oxytocin). In the rat in vitro and in vivo all analogues possessed higher antiuterotonic activity than d(OEt)-oxytocin. The negative logarithm of the molar concentration of the antagonist which reduced the effect of a dose of agonist to that of half the dose (pA2) was between 7.6 and 8.9 for all the new inhibitors compared with 7.2 for d(OEt)-oxytocin. The highest pA2 value was found for 1-deamino-2-Tyr(OMe)-8-Orn-oxytocin (8.9 +/- 0.2, S.E.M.) and 1-deamino-2-Tyr(OEt)-4-Thr-8-Orn-oxytocin (8.9 +/- 0.6). In myometrium from non-pregnant women the most potent peptide was 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin (17.2 +/- 2.0 times more potent that d(OEt)-oxytocin). In myometrium from pregnant women the inhibitory effects of the majority of the analogues were less pronounced.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Pressure; Depression, Chemical; Diuresis; Female; Hormones; Humans; In Vitro Techniques; Myometrium; Oxytocin; Pregnancy; Rats; Uterine Contraction; Vasopressins